scholarly journals A Phase II Safety and Efficacy Study on Prognosis of Moderate Pneumonia in COVID-19 patients with Regular Intravenous Immunoglobulin Therapy

2021 ◽  
Author(s):  
Raman R S ◽  
Vijaykumar Bhagwan Barge ◽  
Anil Kumar Darivenula ◽  
Himanshu Dandu ◽  
Rakesh R Kartha ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Randomized Study ◽  
Standard Of Care ◽  
Immunoglobulin Therapy ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Intravenous Immunoglobulin Therapy ◽  
Safety And Efficacy ◽  
Therapeutic Benefits ◽  
Wide Range

Abstract Background Currently, there is no specific drug for the treatment of COVID-19. Therapeutic benefits of intravenous immunoglobin (IVIG) have been demonstrated in wide range of diseases. The present study is conducted to evaluate the safety and efficacy of IVIG in the treatment of COVID-19 patients with moderate pneumonia. Methods An open-label, multicenter, comparative, randomized study was conducted on COVID-19 patients with moderate pneumonia. 100 eligible patients were randomized in 1:1 ratio either to receive IVIG + standard of care (SOC) or SOC. Results Duration of hospital stay was significantly shorter in IVIG group to that of SOC alone (7.7 Vs. 17.5 days). Duration for normalization of body temperature, oxygen saturation and mechanical ventilation were significantly shorter in IVIG compared to SOC. Percentages of patients on mechanical ventilation in two groups were not significantly different (24% Vs. 38%). Median time to RT-PCR negativity was significantly shorter with IVIG than SOC (7 Vs.18 days). There were only mild to moderate adverse events in both groups except for one patient (2%), who died in SOC. Conclusions IVIG was safe and efficacious as an adjuvant with other antiviral drugs in the treatment of COVID-19. The trial was registered under Clinical Trial Registry, India (CTRI/2020/06/026222).

Safety and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) for locally recurrent or metastatic breast cancer (LR/mBC): Analysis of MO19391 according to CT

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1033-1033
Author(s):  
J. Pierga ◽  
K. I. Pritchard ◽  
C. Thomssen ◽  
H. Cortes-Funes ◽  
L. Biganzoli ◽  
...  
Keyword(s):  
Metastatic Breast ◽  
Standard Of Care ◽  
First Line ◽  
Cns Metastases ◽  
Her2 Positive ◽  
Open Label ◽  
Safety And Efficacy ◽  
First Line Therapy ◽  
Wide Range ◽  
Baseline Characteristics

1033 Background: Combination of B with first-line paclitaxel (TP) or docetaxel (TD) significantly improves PFS vs taxane alone in pts with LR/mBC. The open-label, multicenter MO19391 trial further assessed safety and efficacy of first-line B plus a taxane in >2,000 pts in routine clinical practice. Methods: Eligible pts had HER2- negative LR/mBC (or HER2-positive LR/mBC progressing after trastuzumab-containing therapy), ECOG PS 0–2, no prior CT for LR/mBC and no evidence of CNS metastases. Pts received B 10mg/kg q2w or 15mg/kg q3w plus the physician's choice of taxane (TP or TD alone or with another CT) or other non-anthracycline CT according to physician's standard of care. Treatment was continued until disease progression, unacceptable toxicity, or refusal. The primary endpoint was safety (NCI CTCAE v3.0); secondary endpoints included TTP, OS, and safety in pts developing CNS metastases. Results: From Sept 2006 to June 2008, 2,027 pts from 37 countries were enrolled. Median follow-up is 7.4 months. CT included a taxane (alone or with CT) in ∼75% of pts. Non-taxane agents included capecitabine (X) and vinorelbine (V). In the overall population, median age was 54 years (range 21–93), 70% were ER and/or PgR positive, and 32% had disease-free interval (DFI) ≤24 months. Baseline characteristics were broadly similar across subgroups. However, the X monotherapy subgroup included fewer pts with >3 metastatic lesions and more with a DFI ≤24 months and/or triple-negative disease compared with other subgroups. Safety and efficacy results grouped by CT are shown below. OS data are still immature (85% of pts alive at this analysis). Conclusions: In this large phase IV study, safety and efficacy of B plus TP or TD was similar to results of E2100 and AVADO. Variations in toxicities were consistent with the known profiles of each CT and no new safety signals for B were observed. The lowest incidences of serious Aes were seen with B plus TP or X. TTP was shorter with X and non-taxane combinations. Such findings are potentially attributable to small pt numbers and differences in baseline characteristics. These results show that B can be safely and effectively combined with a wide range of commonly used CT regimens as first-line therapy for mBC. [Table: see text] [Table: see text]

scholarly journals COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Karin Welén ◽  
Anna K Överby ◽  
Clas Ahlm ◽  
Eva Freyhult ◽  
David Robinsson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Virus Disease ◽  
Controlled Trial ◽  
Scale Up ◽  
Standard Of Care ◽  
University Hospital ◽  
Ordinal Scale ◽  
Open Label ◽  
Full Protocol ◽  
Exploration Phase

Abstract Objectives The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. Trial design Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. Participants Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. Intervention and comparator Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. Main outcomes The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). Randomisation Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + “standard of care”: “standard of care”). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) Blinding (masking) This is an open-label trial. Numbers to be randomised (sample size) The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. Trial Status The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. Trial registration Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601, registered June 8, 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.

scholarly journals Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2021 ◽  
Author(s):  
Peter W Horby ◽  
Guilherme Pessoa-Amorim ◽  
Natalie Staplin ◽  
Jonathan R Emberson ◽  
Enti Spata ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Invasive Mechanical Ventilation ◽  
Standard Of Care ◽  
Open Label ◽  
Absolute Increase ◽  
Significant Difference ◽  
Randomised Controlled ◽  
To Receive

Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus 150mg aspirin once daily until discharge using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0.96; 95% confidence interval [CI] 0.89-1.04; p=0.35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days vs. 9 days) and a higher proportion were discharged from hospital alive within 28 days (75% vs. 74%; rate ratio 1.06; 95% CI 1.02-1.10; p=0.0062). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0.96; 95% CI 0.90-1.03; p=0.23). Aspirin use was associated with an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in clinically significant bleeding of 0.6% (SE 0.2%). Interpretation: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death but was associated with a small increase in the rate of being discharged alive.

scholarly journals Rationale and Design of a Phase IIb/III Open-Label, Multicenter Study of Dabigatran Etexilate for Venous Thromboembolism in Children: The Diversity Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5025-5025
Author(s):  
Manuela Albisetti ◽  
Ivan Manastirski ◽  
Martina Brueckmann ◽  
Savion Gropper ◽  
Bushi Wang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Period ◽  
Working Group ◽  
Dabigatran Etexilate ◽  
Plasma Concentrations ◽  
Standard Of Care ◽  
Open Label ◽  
Safety And Efficacy ◽  
Parenteral Treatment ◽  
Expert Working Group

Abstract Background Venous thromboembolism (VTE) is increasing in children. The current standard of care comprises unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for at least 5 days followed by UFH, LMWH or Vitamin K antagonists (VKA) for approximately 3 months in general. All of the current options have limitations: UFH and LMWH require parenteral administration; VKA requires frequent international normalized ratio (INR) monitoring and is associated with multiple food and drug interactions. The direct thrombin inhibitor, dabigatran, which is orally administered as the prodrug, dabigatran etexilate (DE) is effective for the treatment of VTE in adults and may overcome some of the limitations associated with standard of care. Objective To describe the design of a study evaluating the appropriateness of a proposed DE dosing algorithm and assessing the safety and efficacy of DE versus standard of care in pediatric patients with VTE. Methods This open-label, randomized, parallel-group, active-controlled, multi-center, non-inferiority study (NCT01895777) will be conducted in approximately 100 sites in approximately 30 countries. Patients aged 0 to < 18 years with an imaging-confirmed diagnosis of VTE initially receiving parenteral treatment with UFH or LMWH for 5-7 days (but no more than 21 days) who are expected to require anticoagulation therapy for at least 3 months will be eligible for inclusion. Main exclusion criteria include conditions associated with an increased risk of bleeding, renal dysfunction, active infective endocarditis, mechanical or biological heart valve prosthesis, hepatic disease and anemia or thrombocytopenia. Patients will be stratified into three age groups: stratum 1 (12 to < 18 years), stratum 2 (2 to < 12 years) and stratum 3 (birth to < 2 years). Recruitment will begin in stratum 1, being subsequently escalated to strata 2 and 3, respectively based on recommendations from the Data Monitoring Committee. Patients will be randomized (2:1) to receive DE versus standard of care (LMWH or VKA). DE will be administered twice daily as capsules, pellets or an oral liquid formulation depending on patient age and the patient's ability to swallow pellets or capsules. Upon completion of a 3-month treatment period (including the initial parenteral treatment phase) patients will be followed off-study drug for any adverse events. DE will be dosed to achieve steady-state measured trough circulating plasma concentrations (≥50 and < 250 ng/mL); the initial dose required will be calculated using a nomogram, which adjusts dosing according to the age and weight of the child. Dabigatran plasma concentrations will be evaluated at all study visits (7 scheduled during treatment period); DE will be up- or down-titrated as required. Results In terms of efficacy, the study will evaluate the proportion of patients with complete thrombus resolution, freedom from recurrent VTE (including symptomatic and asymptomatic, contiguous progression or non-contiguous new thrombus, deep vein thrombosis, pulmonary and paradoxical embolism, and thrombus progression) and freedom from VTE-related mortality. With regards to safety, the key endpoint will be freedom from major bleeding events, as per International Society on thrombosis and Haemostasis (ISTH) pediatric-specific criteria. All components of the primary efficacy and key safety endpoints will be adjudicated by an independent blinded committee. Conclusion This study, one of the largest controlled pediatric studies for VTE, will provide data on the safety and efficacy of DE compared with standard of care for the treatment of VTE in children aged 0 to < 18 years. Disclosures Albisetti: Boehringer Ingelheim: Other: Pediatric Expert Working Group. Manastirski:Boehringer Ingelheim: Employment. Brueckmann:Boehringer Ingelheim: Employment. Gropper:Boehringer Ingelheim: Employment. Wang:Boehringer Ingelheim: Employment. Tartakovsky:Boehringer Ingelheim: Employment. Biss:Boehringer Ingelheim: Employment. Huang:Boehringer Ingelheim: Employment. Mitchell:Boehringer Ingelheim: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy. Halton:Boehringer Ingelheim: Other: Pediatric Expert Working Group for Boehringer Ingelheim.

scholarly journals Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2020 ◽  
Author(s):  
Peter W Horby ◽  
Alistair Roddick ◽  
Enti Spata ◽  
Natalie Staplin ◽  
Jonathan R Emberson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Invasive Mechanical Ventilation ◽  
Composite Endpoint ◽  
Standard Of Care ◽  
Open Label ◽  
Hospitalised Patients ◽  
Randomised Controlled ◽  
To Receive

Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. Findings: Between 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1.00; 95% confidence interval [CI] 0.90-1.12; p=0.99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1.03; 95% CI 0.97-1.10; p=0.29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0.97; 95% CI 0.89-1.07; p=0.54). Interpretation: In patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication.

A phase 3, open-label, randomized study of nivolumab plus ipilimumab or standard of care (SOC) versus SOC alone in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC; CheckMate 901).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS539-TPS539 ◽  
Author(s):  
Matt D. Galsky ◽  
Thomas Powles ◽  
Shengting Li ◽  
Delphine Hennicken ◽  
Guru Sonpavde
Keyword(s):  
Randomized Study ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Clinical Activity ◽  
Open Label ◽  
Phase 3 ◽  
Tumor Biopsy ◽  
Primary Endpoints ◽  
Platinum Based Chemotherapy ◽  
Independent Review

TPS539 Background: Cisplatin-containing regimens have been SOC for mUC for nearly 40 years, but durable responses are rare with such treatments. Furthermore, a large proportion of pts with unresectable/mUC are ineligible for cisplatin therapy. Treatment approaches conferring longer-term disease control and extending to broader mUC pt populations are urgently needed. Recently, the programmed death-1 (PD-1) inhibitor, nivolumab, induced durable responses in pts with unresectable/mUC progressing despite platinum-based chemotherapy, and nivolumab combined with ipilimumab (a CTLA-4 inhibitor) demonstrated acceptable safety and clinical activity. This phase 3 study will evaluate nivolumab + ipilimumab and nivolumab + SOC vs SOC in previously untreated pts with unresectable/mUC (NCT03036098). Methods: Key inclusion criteria: cisplatin-eligible and -ineligible pts with measurable disease, no prior systemic chemotherapy for unresectable/mUC, and evaluable tumor biopsy. Key exclusion criteria: active brain metastases, autoimmune disease, and prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways. Cisplatin-eligible and -ineligible pts will be randomized 1:1 to arm A (nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks up to 4 doses, followed by nivolumab 480 mg every 4 weeks until disease progression or unacceptable toxicity) or arm B (gemcitabine-cisplatin or gemcitabine-carboplatin for up to 6 cycles). Additional cisplatin-eligible pts will be randomized to arm C (nivolumab 360 mg + gemcitabine-cisplatin every 3 weeks for up to 6 cycles, followed by nivolumab 480 mg) or arm D (gemcitabine-cisplatin for up to 6 cycles). Stratification factors: PD-1 ligand 1 status, cisplatin eligibility, and liver metastasis. Co-primary endpoints: overall and progression-free survival (OS and PFS) by blinded independent review committee (BIRC) in cisplatin-ineligible pts receiving nivolumab + ipilimumab vs SOC, and PFS by BIRC in cisplatin-eligible pts receiving nivolumab + SOC vs SOC. Enrollment began March 2017 with a target of 897 pts. Clinical trial information: NCT03036098.

scholarly journals 517. Subcutaneous Sarilumab for the Treatment of Hospitalized patients with Moderate to Severe COVID19 Disease: A Pragmatic, Embedded, Multi-Center Randomized Clinical Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S360-S360
Author(s):  
Westyn Branch-Elliman ◽  
Ryan Ferguson ◽  
Gheorghe Doros ◽  
Patricia Woods ◽  
Sarah Leatherman ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Healthcare System ◽  
Standard Care ◽  
Point Of Care ◽  
Data Monitoring Committee ◽  
Panel Member ◽  
Standard Of Care ◽  
Hospitalized Patients ◽  
Open Label ◽  
Learning Healthcare System

Abstract Background The aim of this pragmatic, embedded adaptive trial was to measure the effectiveness of subcutaneous sarilumab in addition to an evolving standard of care for clinical management of inpatients with moderate to severe COVID-19 disease (NCT04359901). The study is also a real-world demonstration of the realization of a prospective learning healthcare system. Methods Two-arm, randomized, open-label controlled 5-center trial comparing standard care alone to standard care (SOC), which evolved over time, with addition of subcutaneous sarilumab (200 mg or 400 mg anti-IL6R) among hospitalized patients with moderate to severe COVID-19 not requiring mechanical ventilation. The primary outcome was 14-day incidence of intubation or death. The trial used a randomized play-the-winner design and was fully embedded within the EHR system, including the adaptive randomization process. Results Among 417 patients screened, 162 were eligible based on chart review, 53 consented, and 50 were evaluated for the primary endpoint of intubation or death ( &gt;30% of eligible patients enrolled) (Figure 1). After the second interim review, the unblinded Data Monitoring Committee recommended that the study be stopped due to concern for safety: a high probability that rates of intubation or death were higher with addition of sarilumab to SOC (92.6%), and a very low probability (3.4%) that sarilumab would be found to be superior. Figure 1. Key Study Milestones, Outcomes, and Adaptations Conclusion This randomized trial of patients hospitalized with COVID-19 and requiring supplemental oxygen but not mechanical ventilation found no evidence of benefit from subcutaneous sarilumab in addition to an evolving standard-of-care. The numbers of patients and events were too low to allow independent conclusions to be drawn, but this study contributes valuable information about the role of subcutaneous IL-6 inhibition in the treatment of patients hospitalized with COVID-19. The major innovation of this trial was the advancement of embedded, point-of-care clinical trials for FDA-approved drugs; this represents a realization of the learning healthcare system. Methods developed and piloted during the conduct of this trial can be used in future investigations to speed the advancement of clinical science. Disclosures Nishant Shah, MD, General Electric (Shareholder)Pfizer, Inc. (Research Grant or Support) Karen Visnaw, RN, Liquidia (Shareholder) Paul Monach, MD,PhD, Celgene (Consultant)ChemoCentryx (Consultant)Kiniksa (Advisor or Review Panel member)

scholarly journals Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

2021 ◽  
Author(s):  
Peter W Horby ◽  
Mark Campbell ◽  
Enti Spata ◽  
Jonathan R Emberson ◽  
Natalie Staplin ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Usual Care ◽  
Rate Ratio ◽  
Invasive Mechanical Ventilation ◽  
Composite Endpoint ◽  
Standard Of Care ◽  
Open Label ◽  
Significant Difference ◽  
Randomised Controlled ◽  
To Receive

Background: Colchicine has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory actions. Methods: In this randomised, controlled, open-label trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus colchicine twice daily for 10 days or until discharge (or one of the other treatment arms) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 27 November 2020 and 4 March 2021, 5610 patients were randomly allocated to receive colchicine and 5730 patients to receive usual care alone. Overall, 1173 (21%) patients allocated to colchicine and 1190 (21%) patients allocated to usual care died within 28 days (rate ratio 1.01; 95% confidence interval [CI] 0.93-1.10; p=0.77). Consistent results were seen in all pre-specified subgroups of patients. There was no significant difference in duration of hospitalisation (median 10 days vs. 10 days) or the proportion of patients discharged from hospital alive within 28 days (70% vs. 70%; rate ratio 0.98; 95% CI 0.94-1.03; p=0.44). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (25% vs. 25%; risk ratio 1.02; 95% CI 0.96-1.09; p=0.47). Interpretation: In adults hospitalised with COVID-19, colchicine was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death.

scholarly journals Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits

2021 ◽  
pp. ASN.2020101541
Author(s):  
Ladan Zand ◽  
S. Vincent Rajkumar ◽  
Nelson Leung ◽  
Sanjeev Sethi ◽  
Mireille El Ters ◽  
...  
Keyword(s):  
Partial Remission ◽  
Monoclonal Gammopathy ◽  
Complete Response ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Serious Adverse Events ◽  
Safety And Efficacy ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
Registration Number

BackgroundTreatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID.MethodsWe evaluated daratumumab’s safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m2 and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months.ResultsOne patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months.ConclusionsDaratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation.Clinical Trial registry name and registration number:Daratumumab in Treatment of PGNMID and C3 GN, NCT03095118

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