A placebo-controlled trial of aprepitant for cough in lung cancer.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Amelie Sylvia Mary Harle ◽  
Jaclyn A Smith ◽  
Alex Molassiotis ◽  
Kimberley Lofthouse ◽  
Rachel Dockry ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Controlled Trial ◽  
Performance Status ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Scale Scores ◽  
Never Smokers ◽  
Neurokinin 1 ◽  
Score Range ◽  
Clinical Trial Information

2 Background: There are no evidence-based therapies for cough in lung cancer (LC).The neurokinin-1 (NK-1) pathway is implicated in cough. Aprepitant is an NK-1 antagonist used as an antiemetic. We assess aprepitant as an antitussive, using objective daytime ambulatory cough monitoring (ACM) as the primary endpoint. Methods: LC patients with a “bothersome” cough were enrolled on an exploratory single-arm randomised double-blind crossover trial and received 125mg aprepitant on day 1 and 80mg on days 2 and 3 or matched placebo capsules. After a 3 day wash out,patients crossed over to placebo or aprepitant for 3 days (days 7-9). They completed ACM and validated subjective cough tools. Results: 20 LC patients were enrolled between 7th Oct 2013-3rd Nov 2014; mean age 66 yrs (SD 7.69); 60% (n=12) female; 70% (n=14) ex, 25% (n=5) current and 5% (n=1) never smokers respectively. 20% (n=4), 55% (n=11) and 25% (n=5) had a performance status of 0, 1 and 2 respectively. The majority (80% n=16) had non-small cell LC; half (n=10) had advanced stage; 20% (n=4) were on anticancer therapy. Daytime cough frequency was 15.9 (95%CI 10.1-28.3 n=19), 12.8 (95% CI 8.7-18.8 n=18) and 16.2 (11.3-23.0 n=19) coughs/hr at baseline, on aprepitant and on placebo respectively: p=0.03. Visual analogue scale scores (range 0-100, high score=worse severity) were 57.0mm (95% CI 47.4-67.2 n=19), 40.8mm, (95%CI 34.3-47.3 n=18), and 49.8mm (95%CI 44.2-55.4 n=19) at baseline, on aprepitant and on placebo respectively: p=0.008. The Manchester Cough in Lung Cancer Scale score (range 1-50, high score = worse cough impact) was 25.2 (95%CI 23.0-28.0 n=19), 19.5 (95%CI 17.8-21.2 n=18) and 21.7 (20.3-23.1 n=18) at baseline, on aprepitant and on placebo respectively: p<0.001.There were no serious adverse events. Conclusions: This is the first trial to assess the efficacy of a novel antitussive using validated subjective and objective cough tools in LC and the first to investigate a centrally acting NK-1 antagonist in humans. Aprepitant treatment was associated with statistically significant improvements in objective and subjective scores. The NK-1 receptors may be key mediators in cough in LC. It is possible to run a robust trial using validated measures with clinically meaningful endpoints in a LC population. Clinical trial information: ISRCTN16200035.

scholarly journals Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e045559
Author(s):  
Xuelei Zhang ◽  
Anxin Wang ◽  
Jing Yu Zhang ◽  
Baixue Jia ◽  
Xiaochuan Huo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Endovascular Treatment ◽  
Functional Outcome ◽  
Acute Ischaemic Stroke ◽  
Controlled Trial ◽  
Intravenous Thrombolysis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ischaemic Injury ◽  
Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

scholarly journals Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

2021 ◽  
Author(s):  
Kathryn E. Stephenson ◽  
Boris Julg ◽  
C. Sabrina Tan ◽  
Rebecca Zash ◽  
Stephen R. Walsh ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Controlled Trial ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Cell Counts ◽  
Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

scholarly journals Corrigendum: Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

2017 ◽  
Vol 3 (2) ◽  
pp. 81-82
Author(s):  
Sabita Uthaya ◽  
Xinxue Liu ◽  
Daphne Babalis ◽  
Caroline Dore ◽  
Jane Warwick ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Analysis Data ◽  
Secondary Outcome ◽  
Final Report ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Correct Treatment ◽  
Data Set ◽  
Study Results ◽  
Made In

Abstract During the uploading of data for submission to the EudraCT results database, a discrepancy was identified. It was noted that the number of deaths per group was not consistent with the number in the final report and trial publication. This discrepancy was found to relate to two randomisation numbers. During the trial, the randomisation database had been held separately from the trial database, with manual transcription of randomisation numbers from the randomisation database to the trial database. Two randomisation numbers had been entered incorrectly into the trial database and, although this was documented at the time, the correction had not been made in the analysis data set. The two infants in question received the correct treatment in accordance with their allocation, but were analysed according to the wrong treatment group. Following the identification of this error, all analyses were repeated. It was confirmed that this error had a negligible impact on the study results. Furthermore, the two infants in question had not been included in the primary and secondary outcome analyses, as one had died and the other had withdrawn prior to the primary end-point assessment, so the key study outcomes remain unchanged. The only changes to the results are in the number of serious adverse events and minor changes to the data in demographics tables mostly affecting decimal points and the CONSORT diagram. Our interpretation of the study results remains unchanged.

scholarly journals Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110458
Author(s):  
Mark A. Socinski ◽  
Cornelius F. Waller ◽  
Tazeen Idris ◽  
Igor Bondarenko ◽  
Alexander Luft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Double Blind

Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

A Controlled Trial of Extended-Release Guanfacine and Psychostimulants on Executive Function and ADHD

2018 ◽  
Vol 24 (2) ◽  
pp. 318-325 ◽  
Author(s):  
Judy P. M. van Stralen
Keyword(s):  
Executive Function ◽  
Adverse Events ◽  
Extended Release ◽  
Rating Scale ◽  
Controlled Trial ◽  
Severity Of Illness ◽  
P Value ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Stimulant Therapy

Objective: To evaluate the effectiveness of guanfacine extended-release (GXR) versus placebo as adjunct therapy to usual care stimulant therapy in improving executive function in children aged 6 to 12 years diagnosed with ADHD. Method: In this single center, double-blind placebo-controlled crossover trial, subjects continued to take their psychostimulant and were randomly assigned at baseline to receive active treatment or placebo first. Efficacy measures included Behavioural Rating Inventory of Executive Function (BRIEF-P), ADHD Rating Scale IV (ADHD-RS IV), and Clinical Global Impressions of Severity of Illness (CGI-S) and Improvement (CGI-I) scales. Safety measures included adverse events and vital signs. Results: Significant benefits of GXR plus psychostimulant were observed on BRIEF-P ( p value = .0392), ADHD-RS-IV ( p < .0001), CGI-S ( p = .0007), and CGI-I ( p = .003). There were no serious adverse events and no new safety signals. Conclusion: Use of GXR as adjunctive therapy to stimulant therapy significantly improves executive function in children with ADHD.

Efficacy of a step-down regimen of oral prednisolone in axial spondyloarthritis: result of a double-blind randomized controlled trial (COBRA-AS Study)

Rheumatology ◽  
2020 ◽  
Author(s):  
Debashish Mishra ◽  
Varun Dhir ◽  
G S R S N K Naidu ◽  
Aastha Khullar ◽  
Vishal Kumar ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Oral Prednisolone ◽  
Functional Improvement ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Step Down

Abstract Objectives To evaluate the efficacy and safety of a step-down regimen of oral prednisolone over 24 weeks in patients of axial SpA (axSpA). Methods This proof-of-concept double-blind randomized controlled trial enrolled patients with active axSpA (BASDAI ≥4) having predominantly axial disease (≤1 active joint currently) and inadequate response to NSAIDs. They were randomized to receive either oral prednisolone (n = 32) or placebo (n = 33) at a dose of 60, 40, 30, 20, 15 and 10 mg daily for 1 week each, following which they received 5 mg prednisolone (or placebo) daily for 18 weeks. The primary endpoint was a 50% improvement in the BASDAI (BASDAI50) at week 24. Analysis was intention to treat. Results A BASDAI50 was achieved by 12 of 32 patients (37.5%) in the prednisolone arm and 3 of 33 patients (9.1%) in the placebo arm at 24 weeks [difference 28.4% (95% CI 7.9, 46.7)]. However, there was no difference in achieving a 20 or 40% improvement in the Assessment of SpondyloArthritis international Society response between the groups. Although there was a significant intergroup difference in adjusted ΔBASDAI and ΔAnkylosing Spondylitis Disease Activity Score with CRP at 24 weeks, there was no difference at 12 weeks. There was also no significant difference in ΔBASFI, ΔBAS-G or ΔBASMI at 12 or 24 weeks. No serious adverse events were noted. There was significant weight gain in the first 12 weeks in the prednisolone group vs placebo [0.9 (s.d. 0.4) kg], but not at 24 weeks. Conclusions In this small study, oral prednisolone was efficacious in axSpA in achieving the primary outcome, but many crucial secondary outcomes such as functional improvement were not met. Its impact on bone loss was not studied. Trial registration: CTRI/2018/01/011342.

scholarly journals Influence of Cinnamon on Glycemic Control in Individuals With Prediabetes: A Randomized Controlled Trial

2020 ◽  
Vol 4 (11) ◽  
Author(s):  
Giulio R Romeo ◽  
Junhee Lee ◽  
Christopher M Mulla ◽  
Youngmin Noh ◽  
Casey Holden ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Cost Effective ◽  
Tolerance Test ◽  
Controlled Clinical Trial ◽  
Oral Glucose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Favorable Safety

Abstract Context The identification of adjunct safe, durable, and cost-effective approaches to reduce the progression from prediabetes to type 2 diabetes (T2D) is a clinically relevant, unmet goal. It is unknown whether cinnamon’s glucose-lowering properties can be leveraged in individuals with prediabetes. Objective The objective of this work is to investigate the effects of cinnamon on measures of glucose homeostasis in prediabetes. Design, Setting, Participants, and Intervention This double-blind, placebo-controlled, clinical trial randomly assigned adult individuals meeting any criteria for prediabetes to receive cinnamon 500 mg or placebo thrice daily (n = 27/group). Participants were enrolled and followed at 2 academic centers for 12 weeks. Main Outcome Measures Primary outcome was the between-group difference in fasting plasma glucose (FPG) at 12 weeks from baseline. Secondary end points included the change in 2-hour PG of the oral glucose tolerance test (OGTT), and the change in the PG area under the curve (AUC) derived from the OGTT. Results From a similar baseline, FPG rose after 12 weeks with placebo but remained stable with cinnamon, leading to a mean between-group difference of 5 mg/dL (P &lt; .05). When compared to the respective baseline, cinnamon, but not placebo, resulted in a significant decrease of the AUC PG (P &lt; .001) and of the 2-hour PG of the OGTT (P &lt; .05). There were no serious adverse events in either study group. Conclusions In individuals with prediabetes, 12 weeks of cinnamon supplementation improved FPG and glucose tolerance, with a favorable safety profile. Longer and larger studies should address cinnamon’s effects on the rate of progression from prediabetes to T2D.

Prevention of Opioid-Induced Nausea and Vomiting During Treatment of Moderate to Severe Acute Pain: A Randomized Placebo-Controlled Trial Comparing CL-108 (Hydrocodone 7.5 mg/Acetaminophen 325 mg/Rapid-Release, Low-Dose Promethazine 12.5 mg) with Conventional Hydrocodone 7.5 mg/Acetaminophen 325 mg

Pain Medicine ◽  
2019 ◽  
Vol 20 (12) ◽  
pp. 2528-2538
Author(s):  
John R Zuniga ◽  
Athena S Papas ◽  
Stephen E Daniels ◽  
Kyle Patrick ◽  
Derek D Muse ◽  
...  
Keyword(s):  
Pain Intensity ◽  
Acute Pain ◽  
Low Dose ◽  
Controlled Trial ◽  
Third Molar ◽  
Nausea And Vomiting ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Rapid Release ◽  
Surgical Extraction

Abstract Objectives To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5 mg) with hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP) was used. Methods This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC/APAP, or placebo. Over the next 24 hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24 hours (SPID24). Results Relative to HC/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P &lt; 0.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P &lt; 0.001). There were no unexpected or serious adverse events. Conclusions CL-108 is a safe and effective combination analgesic/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.

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