Clinical trial NCT04345289: Efficacy and Safety of Novel Treatment Options for Adults With COVID-19 Pneumonia
Official title: Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID
Corona Virus Infection
Viral Pneumonia
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality or need of invasive mechanical ventilation
timeFrame: 28 days
Secondary outcomes:
measure: Frequency of adverse events
timeFrame: 90 days
measure: Frequency of severe adverse events
timeFrame: 90 days
measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
timeFrame: 90 days
measure: Ventilator-free days
timeFrame: 28 days
measure: Organ failure-free days
timeFrame: 28 days
measure: Duration of ICU stay
timeFrame: 90 days
measure: Mortality rate
timeFrame: 7, 14, 21, 28 and 90 days
measure: Length of hospital stay
timeFrame: 90 days
measure: Duration of supplemental oxygen
timeFrame: 90 days
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Arhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Gentofte Hospital
city: Herning
country: Denmark
facility: Herning Hospital
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Kolding
country: Denmark
facility: Kolding Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
Study officials:
affiliation: Hvidovre University Hospital
name: Sandra Hansen, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Simone Bastrup Israelsen, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Louise Thorlacius-Ussing, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Karen Brorup Heje Pedersen, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Clara Clausen, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Michaela Tinggaard, MD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Nichlas Hovmand, MD
role: STUDY_DIRECTOR
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