Clincosm LogoSign in Get a demo

CCAP: Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia

Sponsor
Thomas Benfield (Other)
Overall Status
Terminated
CT.gov ID
NCT04345289
Collaborator
(none)
147
Enrollment
12
Locations
2
Arms
10.5
Actual Duration (Months)
12.3
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled trial, which aims to assess the safety and efficacy of treatment with convalescent plasma for patients with moderate-severe COVID-19.

Participants will be randomized 2:1 to two parallel treatment arms: Convalescent plasma, and intravenous 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
  • Biological: Convalescent anti-SARS-CoV-2 plasma
  • Other: Infusion placebo
 Phase 3

Detailed Description

The study is a randomized, double blinded, placebo-controlled, multicenter study with two parallel treatment arms consisting of either convalescent plasma or intravenous placebo. We plan to enroll a total of 1100 patients yielding a statistical power of 80 % to show a 30% 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 2:1 to the parallel treatment arms, and receive either single dose infusion treatment.

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.

As new knowledge of treatment options for COVID-19 have emerged, the treatment arms including sarilumab, baricitininb, hydroxychloroquine and oral placebo have been terminated.

Study Design

Study Type:
Interventional
Actual Enrollment :
147 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Adaptive multi-arm trial comparing convalescent plasma against control group. Interim analyses are included at 300 and 700 included participants to compare the effect and safety of the experimental treatment to control (placebo). The results of the interim analyses are used to decide if the treatments should be discontinued due to either futility or harm. The study is discontinued if either of the predefined stopping criteria are met. 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.Adaptive multi-arm trial comparing convalescent plasma against control group. Interim analyses are included at 300 and 700 included participants to compare the effect and safety of the experimental treatment to control (placebo). The results of the interim analyses are used to decide if the treatments should be discontinued due to either futility or harm. The study is discontinued if either of the predefined stopping criteria are met. 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)
Masking Description:
Both convalescent plasma and placebo will be administered via a colored intravenous line with a colored sleeve disguising the fluid bag. In order to achieve blinding of participants and treating personnel, patients randomized to active treatment will also receive placebo treatment.
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial
Actual Study Start Date :
May 1, 2020
Actual Primary Completion Date :
Mar 16, 2021
Actual Study Completion Date :
Mar 16, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Convalescent plasma

Will receive active treatment with convalescent anti-SARS-CoV-2 plasma (600 ml) as a single dose iv infusion 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 Names:
  • Convalescent plasma

    		•
    Placebo Comparator: Infusion placebo

    Will receive placebo treatment with saline 0.9% (2 x 300 ml) as an iv single dose infusion in addition to standard care.

    Other: Infusion placebo
    Saline 0.9% (600 ml) as an iv single dose infusion

    Outcome Measures

    Primary Outcome Measures

    1. All-cause mortality or need of invasive mechanical ventilation [28 days]

      Composite outcome

    Secondary Outcome Measures

    1. Frequency of adverse events [90 days]

      Number of participants with adverse events with possible relation to study drug

    2. Frequency of severe adverse events [90 days]

      Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines

    3. Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status [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

    4. Ventilator-free days [28 days]

      Number of days without mechanical ventilation

    5. Organ failure-free days [28 days]

      Number of days without organ-failure

    6. Duration of ICU stay [90 days]

      Number of days in ICU

    7. Mortality rate [7, 14, 21, 28 and 90 days]

      Number of deaths by any cause

    8. Length of hospital stay [90 days]

      Days from the date of hospital admission for COVID-19 to the date of discharge

    9. Duration of supplemental oxygen [90 days]

      Days requiring supplement oxygen

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • ≥18 years of age

    • Confirmed COVID-19 infection by presence of SARS-CoV-2 nucleic acid by polymerase chain reaction (PCR)

    • Evidence of pneumonia given by at least one of the following: SpO2 ≤93% on ambient air or PaO2/FiO2 <300 mmHg/40 kPa OR Radiographic findings compatible with COVID-19 pneumonia

    • For women of childbearing potential: Negative pregnancy test and willingness to use contraceptive (consistent with local regulations) during study period

    • Signed Informed Consent Form by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representatives

    Exclusion Criteria:

    • In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment

    • Participating in other drug clinical trials (participation in COVID-19 antiviral trials may be permitted if approved by sponsor)*

    • Pregnant or breastfeeding, positive pregnancy test in a pre-dose examination

    • Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aalborg University Hospital Aalborg Denmark
    2 Aarhus University Hospital Arhus Denmark
    3 Bispebjerg Hospital Copenhagen Denmark
    4 Rigshospitalet Copenhagen Denmark
    5 Herlev Gentofte Hospital Herlev Denmark
    6 Herning Hospital Herning Denmark
    7 Nordsjællands Hospital Hillerød Denmark
    8 Hvidovre Hospital Hvidovre Denmark
    9 Kolding Hospital Kolding Denmark
    10 Odense University Hospital Odense Denmark
    11 Roskilde Hospital Roskilde Denmark
    12 Vejle Hospital Vejle Denmark

    Sponsors and Collaborators

    • Thomas Benfield

    Investigators

    • 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Thomas Benfield, Professor, Hvidovre University Hospital
    ClinicalTrials.gov Identifier:
    NCT04345289
    Other Study ID Numbers:
    • 25032020
    • 2020-001367-88
    First Posted:
    Apr 14, 2020
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:
    Pneumonia
    Coronavirus Infections
    Pneumonia, Viral

    Study Results

    No Results Posted as of Aug 4, 2022