Effects of Licorice on clinical symptoms and laboratory signs in moderately ill patients with pneumonia from COVID-19: A structured summary of a study protocol for a randomized controlled trial

Abstract Objectives We investigate the effects of Licorice (Glycyrrhiza glabra L.) root extract, an anti-inflammatory natural medicine, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single-center, open-label, randomized, clinical trial with parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants Both male and female patients with ≥18 years of age (≥ 35 kg of weight), admitted at the Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas for treatment, screened for the following criteria. Inclusion criteria: 1. Confirmed diagnosis of SARS-CoV-2 infection (via polymerase chain reaction [PCR] and/or antibody test). 2. Presenting as moderate COVID-19 pneumonia (via chest computed tomography (CT) and/or X-ray) requiring hospitalization. 3. Hospitalized ≤48 hours. 4. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm. Exclusion criteria: 1. Underlying diseases, including chronic heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs. 4. Treatment with Investigational and antiviral therapy in a clinical study within one month before randomization. 5. History of allergy to Licorice. 6. Pregnancy and breastfeeding. Intervention and comparator Intervention group: The standard treatment regimen for COVID-19 along with a Licorice-based herbal preparation (D-Reglis ®, Irandarouk Pharmaceutical Company, Iran) at a dose of 760 mg three times a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. Main outcomes The recovery rate of clinical symptoms, including fever, dry cough, and tiredness, as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein, are evaluated as primary outcomes within seven days of randomization. Time to improvement of clinical and paraclinical features and length of stay in a hospital, along with the incidence of adverse reactions are also evaluated as the secondary outcomes within seven days of randomization. Randomization An electronic table of random numbers will be used to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the simple randomization method. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, May 31, 2020. Recruitment began July 30, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N2”, https://www.irct.ir/trial/47990. The registration date is 31 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Evaluation of the effect of melatonin in patients with COVID-19-induced pneumonia admitted to the Intensive Care Unit: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05162-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ali Ameri ◽

Masoomeh Frouz Asadi ◽

Manoochehr Kamali ◽

Majid Vatankhah ◽

Ava Ziaei ◽

...

Keyword(s):

Intensive Care Unit ◽

Mechanical Ventilation ◽

Intensive Care ◽

Standard Treatment ◽

Clinical Symptoms ◽

Intervention Group ◽

Control Group ◽

Open Label ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). Trial design This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding Intervention and Comparator Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education’s protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education’s protocol for a period of seven days. Main outcomes The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. Randomization Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). Trial Status The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. Trial registration The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N7”. The registration date was February 16, 2021. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04934-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Mahsa Miryan ◽

Davood Soleimani ◽

Leila Dehghani ◽

Karim Sohrabi ◽

Farzin Khorvash ◽

...

Keyword(s):

Clinical Trial ◽

Sample Size ◽

Clinical Symptoms ◽

Intervention Group ◽

Trial Registration ◽

Control Group ◽

Double Blind ◽

Double Blind Placebo ◽

Placebo Tablet ◽

Full Protocol

Abstract Objectives This study aims to assess the effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19). Trial design This is a Double-Blind, Placebo-Controlled, Parallel Arm, Randomized Phase ΙΙ Clinical Trial. Participants Patients with the confirmed COVID-19 based on the PCR test are eligible to participate in the trial if they are 18 to 75 years of age and have no history of the current use of warfarin or propolis supplement and presence of sensitivity to bee products. Patients will be recruited from the Al-Zahra hospital in Isfahan city, Isfahan, Iran. Intervention and comparator Participants (N=40) in the intervention group will receive an identical propolis tablet (containing 300 mg Iranian green propolis extract) three times a day for a period of 2 weeks. Participants (N=40) in the control group will receive an identical placebo tablet (containing 300 mg microcrystalline cellulose) three times a day for 2 weeks. All tablets are prepared by the Reyhan Naghsh Jahan Pharmaceutical Co., Isfahan, Iran. Main outcomes The main outcomes are changes in the coronavirus disease’s clinical symptoms including duration and severity from baseline to the end of 2 weeks. Randomization Eligible patients will be randomly allocated in a 1:1 ratio to the intervention or control group. Randomization will be performed on the basis of permuted block sizes of 4 and will be stratified according to sex categories. Randomization sequences will be prepared by the trial’s pharmacist with the use of random-number tables. Blinding (masking) The trial-group assignment will be concealed from all participants, clinicians, and investigators throughout the trial. To ensure blinding, randomization sequences will be kept in identical, opaque, sealed, sequentially numbered envelopes. Only the trial's pharmacist has access to the randomization list. Also, the placebo tablet will be similar to the propolis tablet in terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labelling, and packaging. Numbers to be randomized (sample size) The calculated total sample size is 80 patients, with 40 patients in each group. Trial status The protocol is Version 1.0, October 10, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by March 21, 2021. Trial registration The name of the trial register: The effect of propolis supplementation on clinical symptoms in patients with coronavirus (COVID-19): A randomized, double-blind, placebo-controlled clinical trial. IRCT registration number: IRCT20200802048267N1. Date of trial registration: 20 October 2020, retrospectively registered. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Evaluation of the efficacy and safety of favipiravir and interferon compared to lopinavir/ritonavir and interferon in moderately ill patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04747-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Mehdi Hassaniazad ◽

Ali Bazram ◽

Soheil Hassanipour ◽

Mohammad Fathalipour

Keyword(s):

Interferon Beta ◽

Controlled Trial ◽

Intervention Group ◽

Control Group ◽

List Type ◽

Peptic Ulcers ◽

Efficacy And Safety ◽

Open Label ◽

Full Protocol ◽

Bandar Abbas

Abstract Objectives We will evaluate the efficacy and safety of favipiravir and interferon beta-1a compared to lopinavir/ritonavir and interferon beta-1a in patients with confirmed COVID-19, who are moderately ill. Trial design This is a phase 3, single-center, randomized, open-label, controlled trial with a parallel-group design carried out at Shahid Mohammadi Hospital, Bandar Abbas, Iran. Participants All patients with age ≥ 20 years admitted at the Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria: Confirmed diagnosis of infection with SARS-CoV-2 using polymerase chain reaction and/or antibody tests. Moderate COVID-19 pneumonia (via computed tomography and/or X-ray imaging), requiring hospitalization. Hospitalized ≤ 48 h. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. Exclusion criteria: Underlying conditions, including chronic hepatitis, cirrhosis, cholestatic liver diseases, cholecystitis, peptic ulcers, acute and chronic renal failure, and peptic ulcers. Severe and critical COVID-19 pneumonia. History of allergy to favipiravir, lopinavir/ritonavir, and interferon beta-1a. Pregnancy and breastfeeding. Intervention and comparator Intervention group: favipiravir (Zhejiang Hisun, China) with interferon beta-1a (CinnaGen, Iran). This group will receive 1600 mg favipiravir twice a day for the first day and 600 mg twice a day for the following 4 days with five doses of 44 mcg interferon beta-1a every other day. Control group: lopinavir/ritonavir (Heterd Company, India) with interferon beta-1a (CinnaGen, Iran). This group will receive 200/50 mg lopinavir/ritonavir twice a day for 7 days with five doses of 44 mcg interferon beta-1a every other day. Other supportive and routine care will be the same in both groups. Main outcomes The primary outcome of the trial is the viral load of SARS-CoV-2 in the nasopharyngeal samples assessed by RT-PCR after 7 days of randomization as well as clinical improvement of fever and O2 saturation within 7 days of randomization. The secondary outcomes are the length of hospital stay and the incidence of serious adverse drug reactions within 7 days of randomization. Randomization Eligible patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). A web-based system will be used to generate random numbers for the allocation sequence. Each number relates to one of the study arms. Blinding (masking) This is an open-label trial without blinding and placebo control. Numbers to be randomized (sample size) A total of 60 patients will be randomized into two groups (30 patients in the intervention group and 30 patients in the control group). Trial status The trial protocol is version 1.0, 22 July 2020. Recruitment began on 25 July 2020 and is anticipated to be completed by 25 September 2020. Trial registration Iranian Registry of Clinical Trials (IRCT) IRCT20200506047323N3. Registered on 22 July 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

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A CLINICAL STUDY TO ASSESS THE EFFICACY OF SHWASAHARA DASHEMANI GHANAVATI IN CARDIAC ASTHMA W.S.R L.V.F

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj04p6012021 ◽

2021 ◽

Vol p6 (1) ◽

pp. 3179-3185

Author(s):

Roopa M.R ◽

Vasudev A Chate ◽

Shreevathsa Shreevathsa ◽

Mohan Kumar G

Keyword(s):

Standard Treatment ◽

Intervention Group ◽

Simple Random Sampling ◽

Control Group ◽

P Value ◽

Common Symptom ◽

Open Label ◽

Post Test ◽

Clinically Significant ◽

Cardiac Asthma

Introduction: Shwasa is said as Shigrapranahara Roga. It occurs as the main disease and also a symptom in various diseases. Shwasakruchrata is a common symptom that occurs in Hrudroga. Acharya Charaka mentioned the unique classification of drugs based on their action. Shwasahara Dashemani is one among them. It is containing 10 herbal drugs which are specially indicated in Shwasa Roga. Hence to evaluate the efficacy of Shwasahara Dashemani in Lakshana Roopi Shwasa in L.V.F (Cardiac Asthma) has taken for the study. Aim and Objective: The objective is to assess the efficacy of Shwasahara Dashemani in L.V.F with dyspnea (Cardiac Asthma). Method: The present study is a controlled comparative, open-label, clinical trial with pre and post-test design. A total of 40 subjects of a diagnosed case of L.V.F with dyspnea (Cardiac Asthma) were selected by using a simple random sampling method. Control group subjects were intervened with standard treatment of L.V.F and intervention group subjects were intervened with standard treatment of L.V.F along with Shwasahara Dashemani Ghana Vati, for the duration of 30 days. Its efficacy was assessed before treatment (0th day) and after treatment (31st day) by using BDI (Baseline Dyspnea Index Scale). Results: The P-value of dyspnea of the control group is 1.000 and the P-value of dyspnea of the intervention group is 0.105. This shows that the results of both groups are statistically not significant. But as compared to the control group, the intervention group is clinically significant because after the intervention 35% of subjects had shown improvement in the intervention group. Conclusion: As compared to the control group, in the intervention group Shwasahara Dashemani Ghanavati is clinically significant in relieving cardiac asthma when used with standard treatment of L.V.F. Keyword: Shwasahara Dashemani. Cardiac Asthma, L.V.F, Dyspnea

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Effects of Ginger on clinical manifestations and paraclinical features of patients with Severe Acute Respiratory Syndrome due to COVID-19: A structured summary of a study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04765-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Omid Safa ◽

Mehdi Hassaniazad ◽

Mehdi Farashahinejad ◽

Parivash Davoodian ◽

Habib Dadvand ◽

...

Keyword(s):

Clinical Trial ◽

Severe Acute Respiratory Syndrome ◽

Pharmaceutical Company ◽

Standard Treatment ◽

Clinical Manifestations ◽

Control Group ◽

Exclusion Criteria ◽

Positive Polymerase Chain Reaction ◽

Gi Symptoms ◽

Full Protocol

Abstract Objectives We investigate the effects of Ginger, compared to the usual therapeutic regimen on clinical manifestations and paraclinical features in patients with confirmed COVID-19 that are moderately ill. Trial design This is a single center, randomized, double-blind, placebo-controlled clinical trial with parallel group design. Participants Inclusion criteria: 1. Patients admitted to Severe Acute Respiratory Syndrome (SARS) Departments at Shahid Mohammadi Hospital, Bandar Abbas, Iran 2. Age ≥18 years (weight ≥35 kg) 3. Hospitalized ≤48 hours 4. Confirmed SARS-CoV-2 diagnosis (Positive polymerase chain reaction (PCR)) 5. Moderate pneumonia and lung involvement in imaging 6. Signing informed consent and willingness of study participant to accept randomization to any assigned treatment arm Exclusion criteria: 1. Underlying diseases, including heart disease, chronic hypertension, severe renal failure, severe liver failure, and thyroid disorders 2. Use of warfarin, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), diuretics, corticosteroids, and antiarrhythmic drugs 3. Severe and critical pneumonia 4. History of known allergy to Ginger 5. Pregnancy and breastfeeding Intervention and comparator Intervention group: The standard treatment regimen for COVID-19 along with Ginger-based herbal tablets (Vomigone ®, Dineh Pharmaceutical Company, Iran) at a dose of 1000 mg three times a day for a period of seven days. Control group: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol, along with Vomigone-like placebo tablets (Dineh Pharmaceutical Company, Iran) at a dose of two tablets three times a day for a period of seven days. Main outcomes The primary outcome is recovery rate of clinical symptoms, including fever, dry cough, tiredness, and GI symptoms as well as paraclinical features, including thrombocytopenia, lymphocytopenia, and C-reactive protein within seven days of randomization. Time to improvement of clinical and paraclinical features along with the incidence of serious adverse events are the secondary outcomes within seven days of randomization. Randomization An interactive web-based system will be used to allocate eligible participants, based on the inclusion and exclusion criteria, to one of the two study arms (in a 1:1 ratio) using block randomization. Blinding (masking) All study participants, research coordinators, clinicians, nurses, and investigators will be blinded to the group assignment. Numbers to be randomized (sample size) A total of 84 participants will be randomized into two groups of 42 patients. Trial Status The protocol is Version 1.0, May 23, 2020. Recruitment began July 21, 2020, and is anticipated to be completed by October 30, 2020. Trial registration This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is “IRCT20200506047323N1”. Registration date is 23 May 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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Efficacy of a Chinese Herbal Medicine Compound Zhangpi Ointment against Hydroxyurea-Induced Leg Ulcers: A Prospective, Randomized, Open-Label, Controlled Clinical Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9329465 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8

Author(s):

Yu-yang Pang ◽

Yan Li ◽

Gang Kui ◽

Yong Tang ◽

Ming-juan Liao ◽

...

Keyword(s):

Clinical Trial ◽

Myeloproliferative Neoplasms ◽

Controlled Trial ◽

Intervention Group ◽

Complete Healing ◽

Control Group ◽

Controlled Clinical Trial ◽

Leg Ulcers ◽

Open Label ◽

Chinese Herbal

Objective.The randomized controlled trial was to evaluate the efficacy of topical Chinese herbal Zhangpi Ointment for hydroxyurea-induced leg ulcers in patients with myeloproliferative neoplasms.Patients and Methods.This single-center, prospective, randomized, open-label, controlled clinical trial conducted at Shanghai Ninth People’s Hospital enrolled 54 patients with hydroxyurea-induced leg ulcers. Patients were randomly assigned to the control group (n = 27) treated with chlorhexidine dressing or the intervention group (n = 27) treated with the Zhangpi Ointment. Finally, 26 patients in the control group and 23 patients in the intervention group completed 8 weeks of observation.Results.The rate of complete healing was 100% for the intervention group, which was significantly higher than that of the control group (96.15%) (P<0.05). Furthermore, the intervention group achieved a significantly higher rate of wound healing (95.56%) than the control group (69.02%) at week 4 (P<0.01). The intervention group took 34 ± 5 days to achieve complete healing while the control group took 41 ± 7 days (P< 0.01). Moreover, grade 3/4 side effects were observed in neither group.Conclusion.The Zhangpi Ointment is effective in promoting the healing of hydroxyurea-induced leg ulcers in patients with myeloproliferative neoplasms, providing a therapeutic option for a condition that is recalcitrant to conventional therapy.

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Revisit the Effectiveness of Educational Kinesiology on Stress and Anxiety Amelioration in Kindergarteners With Special Needs: A Nonrandomized Trial

10.21203/rs.3.rs-407301/v1 ◽

2021 ◽

Author(s):

Pui Lun Alan TAI ◽

Kwok Wai Way LAU

Keyword(s):

Clinical Trial ◽

Special Needs ◽

Scientific Evidence ◽

Intervention Group ◽

Control Group ◽

Clinical Trial Registry ◽

Open Label ◽

Post Intervention ◽

Educational Kinesiology ◽

Registration Number

Abstract Although educational kinesiology is a popular intervention aims to improve brain functioning via physical movements, it lacks supporting scientific evidence. This study explores the effect of educational kinesiology on the changes in stress and anxiety markers in kindergarteners with special needs using psychometrics and biological measures. This open label non-randomized clinical trial was registered retrospectively in the Chinese Clinical Trial Registry (registration number: ChiCTR2000036305, url: http://www.chictr.org.cn/showproj.aspx?proj=58067, registration date: 22/08/2020). Thirty-seven kindergarteners with special needs (3.5-6.5 years old) were assigned to either the intervention group, which received one-hour educational kinesiology intervention weekly for a total of 10 weeks, or the wait-list control group. Scores of Parent-rated Preschool Anxiety Scale (PAS-TC), salivary cortisol and oxytocin levels were obtained pre- and post-intervention. After controlling baseline, the changes in oxytocin levels remained significantly different between groups (F1,35 = 5.590, p = 0.020, eta2 = 0.145), but not in cortisol levels (F1,35 = 0.364, p = 0.550, eta2 = 0.01). PAS-TC showed significant improvement in anxiety levels after the intervention in the intervention group (X2 = 4.367, p = 0.037, φ = 0.344, p = 0.037). Findings from both subjective and objective measures indicate a plausible anti-stress and anxiety effect in kindergarteners with special needs.

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Safety and efficacy of hydroxychloroquine for treatment of non-severe COVID-19 among adults in Uganda: a randomized open label phase II clinical trial

BMC Infectious Diseases ◽

10.1186/s12879-021-06897-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Pauline Byakika-Kibwika ◽

Christine Sekaggya-Wiltshire ◽

Jerome Roy Semakula ◽

Jane Nakibuuka ◽

Joseph Musaazi ◽

...

Keyword(s):

Clinical Trial ◽

Viral Load ◽

Adverse Events ◽

Phase Ii ◽

Intervention Group ◽

Viral Clearance ◽

Control Group ◽

Rt Pcr ◽

Open Label ◽

Open Label Phase

Abstract Background Several repurposed drugs such as hydroxychloroquine (HCQ) have been investigated for treatment of COVID-19, but none was confirmed to be efficacious. While in vitro studies have demonstrated antiviral properties of HCQ, data from clinical trials were conflicting regarding its benefit for COVID-19 treatment. Drugs that limit viral replication may be beneficial in the earlier course of the disease thus slowing progression to severe and critical illness. Design We conducted a randomized open label Phase II clinical trial from October–December 2020. Methods Patients diagnosed with COVID-19 using RT-PCR were included in the study if they were 18 years and above and had a diagnosis of COVID-19 made in the last 3 days. Patients were randomized in blocks, to receive either HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days plus standard of care (SOC) treatment or SOC treatment alone. SARS COV-2 viral load (CT values) from RT-PCR testing of samples collected using nasal/orapharyngeal swabs was performed at baseline, day 2, 4, 6, 8 and 10. The primary outcome was median time from randomization to SARS COV-2 viral clearance by day 6. Results Of the 105 participants enrolled, 55 were assigned to the intervention group (HCQ plus SOC) and 50 to the control group (SOC only). Baseline characteristics were similar across treatment arms. Viral clearance did not differ by treatment arm, 20 and 19 participants respectively had SARS COV-2 viral load clearance by day 6 with no significant difference, median (IQR) number of days to viral load clearance between the two groups was 4(3–4) vs 4(2–4): p = 0.457. There were no significant differences in secondary outcomes (symptom resolution and adverse events) between the intervention group and the control group. There were no significant differences in specific adverse events such as elevated alkaline phosphatase, prolonged QTc interval on ECG, among patients in the intervention group as compared to the control group. Conclusion Our results show that HCQ 400 mg twice a day for the first day followed by 200 mg twice daily for the next 4 days was safe but not associated with reduction in viral clearance or symptom resolution among adults with COVID-19 in Uganda. Trial registration: NCT04860284.

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A Randomized Open-Label Trial To Evaluate The Efficacy And Safety Of Triple Therapy With Aspirin, Atorvastatin, And Nicorandil In Hospitalised Patients With SARS Cov-2 Infection: A Structured Summary Of A Study Protocol For A Randomized Controlled Trial

10.21203/rs.3.rs-550553/v1 ◽

2021 ◽

Author(s):

Ambudhar Sharma ◽

Charu Sharma ◽

Sujeet Raina ◽

Balraj singh ◽

Devendra Singh Dadhwal ◽

...

Keyword(s):

Hospital Stay ◽

Hospital Discharge ◽

Intervention Group ◽

Control Group ◽

Open Label ◽

Once Daily ◽

Starting Dose ◽

Full Protocol ◽

Open Label Trial ◽

And Control

Abstract ObjectivesThe pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19.Trial designSingle-centre, prospective, two-arm parallel design, open-label randomized control superiority trial. ParticipantsThe study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included.Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded. Intervention and comparatorAfter randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil. Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines.Main outcomesThe patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D –dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia—muscle ache, or weakness without creatine kinase (CK) elevation, myositis—muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis—muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay. RandomizationComputer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only. Blinding (masking)The study will be an open-label trial. Numbers to be randomized (sample size)A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group.Trial statusThe first version of the protocol was approved by the institutional ethical committee on 1st February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021.Trial registrationThe trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 08/04/2021].Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

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Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-020-04409-9 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 4

Author(s):

Pradeesh Sivapalan ◽

Charlotte Suppli Ulrik ◽

Rasmus Dahlin Bojesen ◽

Therese Sophie Lapperre ◽

Josefin Viktoria Eklöf ◽

...

Keyword(s):

Study Protocol ◽

Standard Treatment ◽

Controlled Trial ◽

Intervention Group ◽

Cardiac Conduction ◽

Control Group ◽

Qtc Interval ◽

Patient Will ◽

Full Protocol ◽

Fertile Women

Abstract Objectives The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. Trial design This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. Participants 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. Inclusion criteria: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. Intervention and comparator Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 Main outcomes • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") Randomisation The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). Blinding (masking) Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. Numbers to be randomised (sample size) This study requires 226 patients randomised 1:1 with 113 in each group. Trial Status Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). Trial registration ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

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