DSMB advise due to high probability of futility

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.

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.

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

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.