scholarly journals Evaluation of the Efficacy and Safety of Intravenous Remdesivir in Adult Patients with Severe Pneumonia caused by COVID-19 virus Infection: study protocol for a Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre trial

2020 ◽  
Author(s):  
Peter W Horby ◽  
Bin Cao ◽  
Yeming Wang ◽  
Chen Wang
Keyword(s):  
Virus Infection ◽  
Multicentre Trial ◽  
Severe Pneumonia ◽  
Hubei Province ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

Abstract Background: A novel coronavirus emerged in Wuhan, Hubei Province, China towards the end of 2019 (SARS-CoV-2 or COVID-19 virus). Large scale spread within China and internationally led the World Health Organisation to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in-vitro and in-vivo experiments. It is also inhibitory against the COVID-19 virus in-vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe pneumonia caused by COVID-19 virus infection.Methods: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥18 years) with laboratory confirmed COVID-19 virus infection, and severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenous remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required had been observed.Discussion: This is the first randomized, placebo-controlled trial in 2019-nCoV. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.Trial registration: ClinicalTrials.gov, NCT04257656, 6th February 2020.

scholarly journals Evaluation of the Efficacy and Safety of Intravenous Remdesivir in Adult Patients with Severe Pneumonia caused by COVID-19 virus Infection: study protocol for a Phase 3 Randomized, Double-blind, Placebo-controlled, Multicentre trial

2020 ◽  
Author(s):  
Yeming Wang ◽  
Fei Zhou ◽  
Dingyu Zhang ◽  
Jianping Zhao ◽  
Ronghui Du ◽  
...  
Keyword(s):  
Virus Infection ◽  
Multicentre Trial ◽  
Severe Pneumonia ◽  
Hubei Province ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo

Abstract Background: A novel coronavirus emerged in Wuhan, Hubei Province, China towards the end of 2019 (SARS-CoV-2 or COVID-19 virus). Large scale spread within China and internationally led the World Health Organisation to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including highkly pathogenic MERS-CoV and SARS-CoV, in in-vitro and in-vivo experiments. It is also inhibitory against COVID-19 virus in-vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe pneumonia caused by COVID-19 virus infection.Methods: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥18 years) with laboratory confirmed COVID-19 virus infection, and severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenous remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death). One interim analysis for efficacy and futility will be conducted once half of the total number of events required had been observed.Discussion: This is the first randomized, placebo-controlled trial in 2019-nCoV. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020.

scholarly journals EXPRESS: Efficacy and Safety of Tadalafil in a Pediatric Population with Pulmonary Arterial Hypertension: Phase 3 randomized, Double Blind Placebo-Controlled Study

2021 ◽  
pp. 204589402110249
Author(s):  
David D Ivy ◽  
Damien Bonnet ◽  
Rolf MF Berger ◽  
Gisela Meyer ◽  
Simin Baygani ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Statistical Significance ◽  
Significance Testing ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Statistical Significance Testing ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Treatment Groups ◽  
Pulmonary Arterial

Objective: This study evaluated the efficacy and safety of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH). Methods: This phase-3, international, randomized, multicenter (24 weeks double-blind placebo controlled period; 2-year, open-labelled extension period), add-on (patient’s current endothelin receptor antagonist therapy) study included pediatric patients aged <18 years with PAH. Patients received tadalafil 20 mg or 40 mg based on their weight (Heavy-weight: ≥40 kg; Middle-weight: ≥25—<40 kg) or placebo orally QD for 24 weeks. Primary endpoint was change from baseline in 6-minute walk (6MW) distance in patients aged ≥6 years at Week 24. Sample size was amended from 134 to ≥34 patients, due to serious recruitment challenges. Therefore, statistical significance testing was not performed between treatment groups. Results: Patient demographics and baseline characteristics (N=35; tadalafil=17; placebo=18) were comparable between treatment groups; median age was 14.2 years (6.2 to 17.9 years) and majority (71.4%, n=25) of patients were in HW cohort. Least square mean (SE) changes from baseline in 6MW distance at Week 24 was numerically greater with tadalafil versus placebo (60.48 [20.41] vs 36.60 [20.78] meters; placebo-adjusted mean difference [SD] 23.88 [29.11]). Safety of tadalafil treatment was as expected without any new safety concerns. During study period 1, two patients (1 in each group) discontinued due to investigator’s reported clinical worsening, and no deaths were reported. Conclusions: The statistical significance testing was not performed between the treatment groups due to low sample size, however, the study results show positive trend in improvement in non invasive measurements, commonly utilized by clinicians to evaluate the disease status for children with PAH. Safety of tadalafil treatment was as expected without any new safety signals.

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