Clinically Vulnerable Individuals with Mild COVID-19 MedDRA version: 23.1 Level: LLT Classification code 10084355 Term: COVID-19 virus test positive System Organ Class: 10022891 - Investigations
Conditions
Interventions
Trade Name: Fresh frozen plasma (FFP) with marketing authorisation in Germany
issued by PEI
Pharmaceutical Form: Solution for infusion
Sponsors
DRK-Blutspendedienst Baden-Württemberg - Hessen gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Two patient populations will be included in the study: (1) unvaccinated elderly and high COVID-age population and (2) high-risk immunocompromised population. (1) Unvaccinated elderly and high COVID-age population: 1. SARS-CoV-2 RNA or SARS-CoV-2 antigen detected in a specimen, = 7 days after onset of symptoms 2. Symptoms of COVID-19 (so including but not limited to: fever; cough; breathlessness; chest pain; wheeze; sore throat; haemoptysis; runny nose; fatigue; muscle or joint pain; confusion; headache; seizures; nausea; vomiting; diarrhoea; abdominal pain; poor appetite; skin ulcers or rash; ear pain; conjunctivitis; anosmia; bleeding; lymphadenopathy.52 The attending clinician will determine if symptoms are consistent with COVID-19. 3. Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support 4. Ability to transfuse (per randomisation) within 7 days after onset of symptoms 5. Men or women, 70 years or older OR under 70 years with significant comorbidities (arterial hypertension, diabetes, obesity, asthma or other chronic pulmonary disease, cardiovascular disease, cerebrovascular disease, chronic kidney disease / dialysis, liver disease, chronic neurological disease, rheumatoid arthritis, lupus or psoriasis) resulting in a ‘COVID-age’ of 70 years or more according to the ALAMA risk calculator https://alama.org.uk/covid-19-medical-risk-assessment/ 6. Signed written informed consent (2) High-risk immunocompromised population 1. SARS-CoV-2 RNA or SARS-CoV-2 antigen detected in a specimen, = 7 days after onset of symptoms 2. Symptoms of COVID-19 (so including but not limited to: fever; cough; breathlessness; chest pain; wheeze; sore throat; haemoptysis; runny nose; fatigue; muscle or joint pain; confusion; headache; seizures; nausea; vomiting; diarrhoea; abdominal pain; poor appetite; skin ulcers or rash; ear pain; conjunctivitis; anosmia; bleeding; lymphadenopathy.52 The attending clinician will determine if symptoms are consistent with COVID-19. 3. Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support 4. Ability to transfuse (per randomisation) within 7 days after onset of symptoms 5. Male or female Adult =18 years of age with extremely high risk including: a. Patients with at least one of the following acquired immune deficiencies: i. Lymphoid malignancies treated within the last 12 months ii. Lymphoid malignancies with persistent hypogammaglobulinaemia (IgG < 5 g/L) iii. Myeloid malignancies treated by chemotherapy within the last 12 months iv. Myeloid malignancies treated with anti-BCL-2 drugs within the last 12 months v. Myeloid malignancies associated with prolonged neutropenia (= 6 weeks) vi. Solid tumour undergoing treatment with chemotherapy (until 3 months after completion of the last chemotherapy cycle). vii. Allogenic hematopoietic stem cell transplantation within the last 12 months or anytime if on-going treatment for chronic GVHD viii. Organ transplantation ix. Anti - B (CD20/CD19) MoAb and/or mycophenolate mofetil treatment within the last 12 months x. Anti-CD19/CD20 CAR-T cell treatment xi. ATG or alemtuzumab treatment within the last 6 months xii. AIDS or b. Patients with primary lymphoid immune deficiencies: i. B cell deficiencies (such as Bruton agammaglobulinemia) ii. T cell deficiencies (such as Wiskott Aldrich disease) iii. Combined deficiencies (such as Common variable immunodeficiency ) or c. Patients without detectable s
Exclusion criteria
Exclusion criteria: (1) Unvaccinated elderly and high COVID-age population: 1. Age < 18 years 2. Prior or concurrent treatment for COVID-19 (unless listed as authorized specific treatment in the Appendix) 3. History of documented SARS-CoV-2 infection in the last 90 days prior to enrolment 4. Prior anti-SARS-CoV-2 immunization 5. Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components 6. Known participant objection to receiving plasma products 7. Primary or acquired immune deficiency listed below (see cohort 2) 8. Refusal to participate expressed by patient or legally authorised representative 9. Pregnancy (2) High-risk immunocompromised population 1. Age < 18 years 2. Prior or concurrent treatment for COVID-19 (dexamethasone, anti-IL-6/IL6R, remdesivir) except for prophylactic administration of anti-SARS-Cov2 monoclonal antibodies (pre or post exposure) in cohort 2 and authorized specific treatment in the Appendix) 3. History of documented SARS-CoV-2 infection in the last 90 days prior to enrollment 4. Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components 5. Known participant objection to receiving plasma products 6. Refusal to participate expressed by patient or legally authorised representative 7. Pregnancy Any patient eligible for both cohorts will be included in cohort 2. Enrolment in other trials after reaching the primary end-point is authorised.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of plasma from COVID-19 convalescent donors (COVID-19 convalescent plasma) and standard of care versus standard of care alone in preventing hospitalisation or death by day 28 after randomisation, in clinically vulnerable patients recently infected by SARS-CoV-2. Standard of care therapy may include anti-SARS-CoV-2 specific medication listed as authorized in a dedicated appendix.;Secondary Objective: To evaluate the efficacy of COVID-19 convalescent plasma on: 1. Hospitalisation for severe COVID-19 2. Hospitalisation for severe COVID-19 requiring O2 support 3. All-cause mortality 4. Requirement for supplemental oxygen 5. Requirement for non-invasive ventilation 6. Requirement for mechanical ventilation 7. The change in WHO Clinical Progression Scale score 8. The duration of hospital stay 9. The need for admission to ITU 10. The duration of ITU stay 11. Cases of long COVID-19 symptoms and the time to recovery 12. Health-related quality of life To analyse the safety of COVID-19 convalescent plasma with regard to: 1. SAEs and unexpected AEs 2. Arterial and venous thrombotic events For more information including the exploratory objectives, please refer to the current protocol version;Primary end point(s): Primary endpoint definition: the proportion of patients hospitalised or death by day 28. The primary outcome will be analysed using logistic regression adjusted for randomisation stratification variables (results will be expressed as odds ratios with 95% confidence intervals). Adjustment for major prognostic factors will be considered depending on the evolution of medical knowledge on the prognosis of patients infected by SARS-Cov-2. ;Timepoint(s) of evaluation of this end point: Day 28 after randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include the following: • Proportion of hospitalisation for progressive COVID-19 symptoms, or death (stages 4 to 9 of the WHO scale) • Proportion of hospitalisation for progressive COVID-19 symptoms requiring O2 support, or death (stages 5 to 9 of the WHO scale) • All-cause mortality • Proportion of patients with supplemental oxygen • Proportion of patients with non-invasive ventilation • Proportion of patients with mechanical ventilation • Change in 10-point WHO Clinical Progression Scale score • Duration of hospital admission • Proportion of patients with ITU admission • Duration of ITU admission • Proportion of patients with long COVID-19 symptoms and time to recovery assessed by questionnaire • Participant experience assessed through validated quality of life questionnaires, including EQ-5D, and assessment of long COVID-19 symptoms Safety analysis of intervention Safety endpoints include the following: • Number of serious Adverse Events • Number of Grade 3 and 4 adverse events • Arterial and venous thromboembolic events Exploratory endpoints • Change in SARS-CoV-2 RNA level (Polymerase chain reactione, Cycle Threshold value) in oral or nose/throat swab samples • Change in anti-SARS-CoV-2 spike antibody levels in blood • SARS-CoV-2 whole-genome sequence analysis in oral or nose/throat swab samples • Proportion and clinical characteristics of patients with cultivable virus • Virus sequence variation and cultivability over time ;Timepoint(s) of evaluation of this end point: Secondary endpoints: • Hospitalisation 14 and 28 days after randomisation • Mortality: day 28, 90, 180 after randomisation • Supplemental oxygen: day 14, 28 after randomisation • Ventilation: day 14, 28 after randomisation • ITU: 28 days after randomisation • Long COVID-19 symptoms and Quality of Life: day 28, 180 post randomisation Safety analysis: • SAEs and AE (Grade 3, 4): 72 h after randomisation • Arterial and venous thromboe | — |
Countries
France, Germany, Netherlands, United Kingdom
Contacts
Public ContactSixten Körper
IKT Ulm
Outcome results
None listed