Trial NCT04433910; EudraCT 2020-001310-38
Publication Koerper S, J Clin Invest, 2021 (published paper)
Dates: 2020-08-30 to 2020-12-24
Funding: Public/non profit (Bundesministerium fuer Gesundheit (German Federal Ministry of Health))
Conflict of interest: Yes
| Methods | |
| RCT Blinding: Unblinded | |
| Location :
Multicenter / Germany Follow-up duration (days): 60 | |
| Inclusion criteria | SARS-CoV-2 infection confirmed by PCR (bronchoalveolar lavage, sputum, nasal and/or pharyngeal swap);
age ≥ 18 years and ≤ 75 years; severe disease defined by at least one of the following: a) respiratory rate ≥ 30 breaths / minute under ambient air; b) requirement of any type of ventilation support (defined as supplemental oxygen or non-invasive ventilation or invasive ventilation or ECMO); c) needs treatment on ICU; written informed consent by patient or representative. |
| Exclusion criteria | Accompanying diseases other than COVID-19 with an expected survival time of less than 12 months; previous treatment with any SARS-CoV-2-convalescent plasma; in the opinion of the clinical team, progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatment; Interval > 72 hours since start of mechanical ventilation; not considered eligible for extracorporeal oxygenation support; chronic obstructive lung disease (COPD), stage 4; lung fibrosis with usual interstitial pneumonia pattern in CT and severe emphysema; chronic heart failure NYHA ≥ 3 and/or pre-existing reduction of left ventricular ejection fraction to ≤ 30%; shock of any type requiring ≥ 0.5 μg/kg/min noradrenaline (or equivalent) or requiring more than two types of vasopressor medication for more than 8 hours; liver cirrhosis Child C; liver failure: bilirubin > 5 x upper limit of normal (ULN) and elevation of ALT /AST (at least one >10 x ULN); any history of adverse reactions to plasma proteins; known deficiency of immunoglobulin A; pregnancy; breastfeeding women; volume overload until sufficiently treated; participation in another clinical trial with an investigational medicinal product. |
| Interventions | |
| Treatment
Convalescent plasma 1 transfusion unit on days 1, 3 and 5. Median total volume = 846 ml (IQR 824-855 ml) |
|
| Control
Standard care ( / ) Definition of Standard care: Patients in both groups received other anti-viral treatment and/or supportive treatment according to institutional standard procedures for patients with severe infection with respiratory viruses. Centers were advised to adhere to current recommendations for treatment of severe COVID-19 published by medical societies. | |
| Participants | |
| Randomized 105 participants (n1=53 / n2= 52) | |
| Characteristics of participants N=105 Mean age : NR 77 males Severity : Mild: n=7 / Moderate: n=13/ Severe: n=49 Critical: n=36 | |
| Primary outcome | |
| In the register Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. [ Time Frame: Day 21 ] | |
| In the report Dichotomous composite outcome of survival and no longer requiring ventilation support or ICU treatment and no tachypnea (i.e., respiratory rate <30 breaths/minute) on day 21. | |
| Documents available |
Protocol NR Statistical plan NR Data-sharing stated Unclear |
| Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review |
Some concerns |
| General comment |
In addition to the published journal and pre-print articles, the trial registry and supplementary appendices (including statistical analysis plan) were used in data extraction and assessment of risk of bias. No protocol was available. There were no substantive differences between the prospective registry and the publication in population, procedures or interventions. The primary outcome indicated in registry reflects the primary outcome reported in the paper. Some outcomes from the registry are not reported in the paper. The analysis for this report is based on an interim data-cut off on April 28, 2021. The study achieved its targeted sample size.
This trial was updated on October 6th, 2021 with data from the peer-reviewed journal publication. |