Covid19
Conditions
Brief summary
An effective, widely available, and safe treatment that can decrease the duration, severity and fatality of COVID-19 is urgently needed. Also, in the most affected regions the pressure on health care systems including ventilator support capacity can be a limiting factor for survival. Initial studies including from our group indicate that administering convalescent plasma containing high titers of neutralizing antibodies to COVID-19 patients who are already relatively late during the disease course after hospital admission is not effective, which can be explained by high titers of autologous antibodies present in patients. Thus, the antiviral capacity of convalescent plasma is hypothesized to be best positioned early in the disease course and in patients at increased risk for a severe disease course. If effective, any treatment that decreases the need for hospital admission is very valuable but so far, no COVID-19 treatment has been shown to prevent clinical deterioration when given before patients are admitted to the hospital. Primary objective: To evaluate the efficacy, feasibility and safety following the administration of convalescent plasma (ConvP) as a therapy for outpatients diagnosed with COVID-19 at increased risk for an unfavourable clinical outcome and within 7 days after symptom onset. Study design: This trial is a nationwide multicenter, double blind, randomized controlled trial in the Netherlands. Patients will be randomized between the transfusion of 300mL of convP versus regular fresh frozen plasma (FFP). Patient population: Patients with polymerase chain reaction (PCR) confirmed COVID disease with less than 8 days of symptoms, age 70 or older or 50-69 years with at least 1 additional risk factor for severe COVID-19 are eligible. Intervention: 300mL of convP with a minimum level of neutralizing antibodies. A total of 690 patients will be included. Expected duration of accrual: 18-24 months Duration of follow up :Day 28 for the primary endpoint
Detailed description
Secondary (exploratory) objectives * To evaluate the impact of 300mL convP on mortality * To evaluate the impact of 300mL convP on hospital admission * To evaluate the impact of 300mL convP on admission to ICU * To evaluate the impact of 300mL convP on duration of symptoms * To evaluate the impact of 300mL convP in relation to the age and clinical frailty of the patient
Interventions
BIOLOGICALConvP
Infusion of plasma retrieved from donors with a history of PCR proven symptomatic COVID. Plasma will be administered according to the Erasmus MC KIS protocol regarding the use of blood products
BIOLOGICALFFP
Infusion of thawed non-convalescent plasma Plasma will be administered according to the Erasmus Medical Center quality protocol regarding the use of blood products
Sponsors
Prothya Biosolutions
ZonMw: The Netherlands Organisation for Health Research and Development
Leiden University Medical Center
Erasmus Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* RT-PCR-confirmed COVID-19. * Symptomatic (e.g but not limited to fatigue, fever, cough, dyspnoea, loss of taste or smell, diarrhea, falls or confusion) * 70 years or older OR 50-69 years and 1 or more of the risk factors described in the protocol
Exclusion criteria
* Life expectancy \<28 days in the opinion of the treating physician * Patient or legal representative is unable to provide written informed consent * Symptomatic for 8 days or more * Being admitted to the hospital at the informed consent procedure * Known previous history of transfusion-related acute lung injury * Known Immunoglobulin A (IgA) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Highest disease status | 28 days following transfusion of convP or FFP | Highest disease status on the 5-point ordinal disease severity scale in the convP group will be compared with the FFP group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Age and clinical frailty score | 28 days following transfusion of convP or FFP | Age and clinical frailty score stratified analysis of percentage of primary endpoint following transfusion of convP versus FFP. |
| Percentage of ICU admissions | 28 days following transfusion of convP or FFP | Percentage of ICU admissions in the convP group compared to the FFP group |
| Disease duration in days of symptoms | 28 days following transfusion of convP or FFP | Disease duration in days of symptoms in the convP group compared to the FFP group |
| Percentage of deaths | 28 days following transfusion of convP or FFP | Percentage of deaths in the convP group compared to the FFP group |
| Percentage of hospital admissions | 28 days following transfusion of convP or FFP | Percentage of hospital admissions in the convP group compared to the FFP group |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in proportion of detectable SARS-Cov-2 RT-PCR results | Day 3, 7, 14 and 28 following transfusion of convP or FFP | Change in proportion of detectable SARS-CoV-2 RT-PCR results at day 3, 7, 14 and 28 following transfusion according to the presence of neutralizing antibodies at baseline |
| Highest disease status stratified by presence of neutralizing antibodies and by symptom duration at baseline | 28 days following transfusion of convP or FFP | Analysis of primary endpoint following transfusion of convP versus FFP stratified by the presence of neutralizing antibodies at baseline and by symptom duration at baseline. |
Countries
Netherlands
Outcome results
None listed