Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia (CCAP)
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|ClinicalTrials.gov Identifier: NCT04345289|
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : May 29, 2020
CCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled, multi-stage trial, which aims to assess the safety and efficacy of novel treatment option of moderate-severe COVID-19.
Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo.
Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.
|Condition or disease||Intervention/treatment||Phase|
|COVID Corona Virus Infection Viral Pneumonia||Biological: Convalescent anti-SARS-CoV-2 plasma Drug: Sarilumab Drug: Baricitinib Drug: Hydroxychloroquine Other: Injective placebo Other: Oral placebo||Phase 3|
The study is a randomized, double blinded, placebo-controlled, multicenter, multi-stage study with six parallel treatment arms consisting of either convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo. We plan to enroll 250 patients in each arm, with a total of 1500 patients yielding a statistical power of 81 % to show a 40% relative reduction in risk of mechanical ventilation or death at day 28. Patients with confirmed COVID-19 infection and signs compatible with pneumonia will be enrolled in the study. The participants will be randomized 1:1:1:1:1:1 to the parallel treatment arms, and depending on the randomization receive either single dose injection/infusion treatment or oral treatment for 7 days.
The primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days. Interim analysis will be performed frequently. We will apply a win ratio matched approach to evaluate the primary endpoint
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1500 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
Adaptive multi-arm trial comparing several different experimental treatments against two control groups. Interim analyses are included at 75 and 175 matched participants to compare the effect and safety of each experimental treatment to control (placebo). The results of the interim analyses are used to decide if one or more treatments should be discontinued due to either futility or harm. An arm is discontinued if either of the predefined stopping criteria are met. For the remaining arms, further patients are recruited until a decision has been reached or until a maximum number of patients is reached.
Additional experimental treatments may be added as they become available. Any efficacious treatment identified in this or any other high-quality RCT may become the new SOC after consensus by national and international societies, and, thus, the control arm will change accordingly and in parallel.
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
Infusion treatment (convalescent plasma and placebo) will be administered via a colored intravenous line with a colored sleeve disguising the fluid bag. Injective treatment (sarilumab and placebo) will be administered in a prepared syringe. Oral treatment (hydroxychloroquine, baricitinib placebo and active treatment) will be prepared in non-identifiable and identical capsules.
In order to achieve blinding of participants and treating personnel, patients randomized to active treatment will also receive placebo treatment.
|Official Title:||Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multi-stage, 6-armed Placebo-controlled Trial in the Framework of an Adaptive Trial Platform|
|Actual Study Start Date :||May 1, 2020|
|Estimated Primary Completion Date :||June 15, 2021|
|Estimated Study Completion Date :||June 15, 2021|
Active Comparator: Convalescent plasma
Will receive active treatment with convalescent anti-SARS-CoV-2 plasma (600 ml) as a single dose iv infusion + placebo treatment with saline 0.9% (1.14 mL) as a single sc injection, in addition to standard care.
Biological: Convalescent anti-SARS-CoV-2 plasma
Single infusion of convalescent anti-SARS-CoV-2 plasma (2 x 300 mL)
Other Name: Convalescent plasma
Active Comparator: Sarilumab
Will receive active treatment with sarilumab (200 mg) as a single sc injection + placebo treatment with saline 0.9% (600 ml) as a single dose iv infusion, in addition to standard care.
Pre-filled syringe 200 mg (1.14 mL) as a single dose
Other Name: Kevazara
Placebo Comparator: Injective placebo
Will receive placebo treatment with saline 0.9% (600 ml) as an iv single dose infusion + placebo treatment with saline 0.9% (1.14 mL) as a single sc injection, in addition to standard care.
Other: Injective placebo
Saline 0.9% (600 ml) as an iv single dose infusion + placebo treatment with saline 0.9% (1.14 mL) as a single sc injection
Active Comparator: Hydroxychloroquine
Will receive active treatment with hydroxychloroquine (600 mg) as a daily oral administration for 7 days in addition to standard care.
Tablets 600 mg/day for 7 days
Other Name: Plaquenil
Active Comparator: Baricitinib
Will receive active treatment with baricitinib (4 mg) as oral administration for 7 days + oral placebo treatment for 7 days, in addition to standard care.
Tablets 4 mg/day for 7 days
Other Name: Olumiant
Placebo Comparator: Oral placebo
Will receive placebo treatment with three glucose monohydrate placebo capsules daily for 7 days, in addition to standard care.
Other: Oral placebo
Three glucose monohydrate placebo capsules daily for 7 days
- All-cause mortality or need of invasive mechanical ventilation [ Time Frame: 28 days ]Composite outcome
- Frequency of adverse events [ Time Frame: 90 days ]Number of participants with adverse events with possible relation to study drug
- Frequency of severe adverse events [ Time Frame: 90 days ]Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
- Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status [ Time Frame: 90 days ]Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities
- Ventilator-free days [ Time Frame: 28 days ]Number of days without mechanical ventilation
- Organ failure-free days [ Time Frame: 28 days ]Number of days without organ-failure
- Duration of ICU stay [ Time Frame: 90 days ]Number of days in ICU
- Mortality rate [ Time Frame: 7, 14, 21, 28 and 90 days ]Number of deaths by any cause
- Length of hospital stay [ Time Frame: 90 days ]Days from the date of hospital admission for COVID-19 to the date of discharge
- Duration of supplemental oxygen [ Time Frame: 90 days ]Days requiring supplement oxygen
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04345289
|Contact: Thomas Benfield, MD, DMSc||+45 firstname.lastname@example.org|
|Aalborg University Hospital||Not yet recruiting|
|Contact: Henrik Nielsen, MD, DMSc|
|Aarhus University Hospital||Not yet recruiting|
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|Kolding Hospital||Not yet recruiting|
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|Contact: Isik Johansen, MD, DMSc email@example.com|
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|Vejle Hospital||Not yet recruiting|
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|Study Director:||Sandra Hansen, MD||Hvidovre University Hospital|
|Study Director:||Simone Bastrup Israelsen, MD||Hvidovre University Hospital|
|Study Director:||Louise Thorlacius-Ussing, MD||Hvidovre University Hospital|
|Study Director:||Karen Brorup Heje Pedersen, MD||Hvidovre University Hospital|
|Study Director:||Clara Clausen, MD||Hvidovre University Hospital|
|Study Director:||Michaela Tinggaard, MD||Hvidovre University Hospital|
|Study Director:||Nichlas Hovmand, MD||Hvidovre University Hospital|