No registrations found.
ID
Source
Brief title
Health condition
COVID-19
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ordinal outcome at day 14 of all cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay (6 days or more), with less than 6 hospitalized days as reference category.
Secondary outcome
assessment of the primairy ordinal outcome at day 21, 28 and 56; combined outcome of death and ICU admission at day 14, 21, 28 and 56; duration of hospitalization in days; length of stay in ICU; and ICU mortality.
- The following safety parameters will be assessed during this trial: deterioration of respiratory, circulatory or otherwise the clinical status during transfusion; transfusion transmitted infections.
- The time until negative SARS-CoV-2 PCR (nasal/ pharyngeal swab)
Background summary
This is a randomized, prospective, multicenter, double blinded phase 2/3 trial comparing efficacy and safety of anti-SARS-CoV-2 convalescent plasma vs standard plasma in maximally 3 days hospitalized COVID-19 patients that are not at or bound to be referred to the ICU.
In the described context of possible benefits but still uncertain risks, we on purpose perform a double blinded phase 2/3 RCT to investigate both safety and effectivity of early in the disease course administrated convalescent plasma in patients with COVID-19. The latter patients are sick enough to warrant hospitalization but have not (yet) experienced overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS warranting ventilation and (eminent) ICU referral.
Study population:
This study will enrol adult patients with confirmed COVID-19 infection, who have been recently (not more than 3 days) hospitalized, but are not admitted to the ICU or expected to go to the ICU within 6 hours of first plasma administration.
Intervention:
Enrolled patients will either receive convalescent thawed fresh frozen plasma 1 unit (250-325 ml) (=treatment group) or standard thawed fresh frozen plasma 1 unit (250-325 ml) (=control group)
Study endpoints:
The estimated benefit in regard of the primary endpoint is a shift in the distribution of the scores towards less mortality, mechanical ventilation, ICU admission and shorter than the presently mean hospital stay (see figure). The primary endpoint will be analyzed using a Bayesian proportional odds model. Posterior probabilities will start to be computed after 20 patients have completed their follow-up and will be computed on regular basis afterwards.
The endpoints can be summarized as following:
= Ordinal outcome of all cause mortality, mechanical ventilation, ICU admission and long duration of hospital stay (6 days or more), with less than 6 hospitalized days as reference category will be used for the primary outcome. The outcome will be primarily assessed at day 14.
- The following other efficacy parameters will be assessed as a secondary outcome: assessment of the primairy ordinal outcome at day 21, 28 and 56; combined outcome of death and ICU admission at day 14, 21, 28 and 56; duration of hospitalization in days; length of stay in ICU; and ICU mortality.
- The following safety parameters will be assessed during this trial: deterioration of respiratory, circulatory or otherwise the clinical status during transfusion; transfusion transmitted infections.
- The time until negative SARS-CoV-2 PCR (nasal/ pharyngeal swab)
Study objective
Convalescent plasma of ex-COVID-19 patients will improve outcome of recently admitted patients with active disease but not (yet) at ICU.
Study design
days 1,2,3,7,14,21,28,56
Intervention
Enrolled patients will either receive convalescent thawed fresh frozen plasma 1 unit (250-325 ml) (=treatment group) or standard thawed fresh frozen plasma 1 unit (250-325 ml) (=control group)
Inclusion criteria
1. Maximal 3 days hospitalized at plasma infusion.
2. Age ≥ 18 years and ≤ 85 years
3. SARS-CoV-2 infection: confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap) not longer than 7 days before.
4. Symptoms not expected to lead to IC transfer within 6 hours of study plasma administration
5. Written informed consent including storing of specimen for future testing
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
1. Accompanying diseases other than COVID-19 with an expected survival time of less than 6 months
2. Chronic severe pulmonary dysfunction like obstructive lung disease (COPD), Gold stage 4; severe emphysema; or lung fibrosis with usual interstitial pneumonia (IUP) pattern
3. Chronic heart failure NYHA >= 3 and/or pre-existing reduction of left ventricular ejection fraction to ≤ 30% for which among others e.g. strict fluid restriction is needed
4. Clinical diagnosis of circulatory overload for which active therapy (like increased doses of diuretics) is initiated
5. Clinical judgement of deterioration in oxygenation (e.g. more than 2 L increase in additonal O2 by nose tube), respiratory rates ( e.g. more than 5 / min increase) in the 2 hours before the planned randomisation / plasma infusion
6. Signs of severe coagulopathy : thrombocytopenia by consumption ( <100 x 10e9/l) or prolongation of the PT (+3 sec) , PTT (+ 5 sec)
7. Any history of severe adverse reactions to plasma proteins
8. Known deficiency of immunoglobulin A
9. Pregnancy
10. Breastfeeding women
11. Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL8633 |
| CCMO | NL73791.058.20 |
| OMON | NL-OMON49946 |