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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001310-38 | EudraCT Number |
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This is a randomized, prospective, multicenter, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.
The aim of the study is to explore the therapeutic effect of convalescent plasma transfusions on the survival and course of disease of patients with severe COVID-19. Convalescent plasma will be collected from recovered COVID-19 patients.
Patients with severe COVID-19 will be randomly assigned to two groups. Patients in the treatment group will receive covalescent plasma (250 - 325 ml) on days 1, 3 and 5. Patients in the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline, patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19.
Fifty-three patients will be included in each group. Data of each patient will be collected until discharge but nor longer than day 60.
This is a randomized, prospective, multicentre, open label clinical trial of convalescent plasma compared to best supportive care for treatment of patients with severe COVID-19.
The primary Endpoint is a dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19 within 21 days after randomization. All criteria must be met in order to fulfil the primary endpoint.
Key secondary endpoints are time to clinical improvement (defined as time from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement), the frequency and severity of adverse events and the case fatality rate on day 21, 35 and 60. Further secondary endpoints refer to the course of anti-SARS-CoV-2 antibodies in plasma donors and treated patients and the impact of donor criteria on the effectiveness of plasma units.
Patients with severe COVID-19 defined by a respiratory rate ≥ 30 breaths / minute under ambient air or the requirement of any type of ventilation support or the need for ICU treatment can be included in the trial. It is planned to enrol 106 patients. Patients will be stratified according to ventilation support and/or extracorporeal oxygenation and/or ICU treatment and will be equally asigned to two groups. The treatment group receives convalescent plasma (250 - 325 ml) on day 1, 3 and 5 and the control group will receive best supportive care. Clinical condition in all patients will be evaluated on day 14. In case of progressive COVID-19 on day 14 compared to baseline (i.e. day 0), patients in the control group may be switched to treatment with convalescent plasma on days 15, 17 and 19. A patient switching from the control group to convalescent plasma group because of progressive COVID-19 on day 14 will be considered as failure of the primary endpoint at final evaluation of the primary endpoint on day 21.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Convalescent plasma | Experimental | Convalescent plasma transfusion on day 1, 3 and 5. |
|
| Best supportive care | No Intervention | Best supportive care, cross over for patients with progressive disease on day 14 with convalescent plasma transfusion on day 15, 17 and 19. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Convalesscent Plasma | Drug | Transfusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. | Dichotomous composite endpoint of survival and no longer fulfilling criteria of severe COVID-19. All criteria must be met in order to fulfil the primary endpoint. | Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to clinical improvement | Time to clinical improvement (defined as days from randomization to an improvement of two points on the WHO R&D Blueprint seven-category ordinal scale for clinical improvement) (Key secondary endpoint) | day 0 to discharge within a 60 day period |
| Frequency and severity of adverse events by CTCAE v5.0, (Key secondary endpoint) |
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Inclusion Criteria:
Patients with SARS-CoV-2 infection and
age ≥ 18 years and ≤ 75 years
SARS-CoV-2 infection confirmed by PCR (BAL, sputum, nasal and/or pharyngeal swap)
severe disease defined by at least one of the following:
Written informed consent by patient or legally authorized representative
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hubert Schrezenmeier, Prof.Dr. | IKT Ulm | Principal Investigator |
| Erhard Seifried, Prof.Dr.Dr. | German Red Cross Blood Service | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Ulm | Ulm | Baden-Württmberg | 89081 | Germany | ||
| University Hopsital Frankfurt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37162745 | Derived | Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 May 10;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub6. | |
| 36734509 |
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| day 0 to discharge within a 60 day period |
| Case fatality rate | on day 21, 35 and 60 |
| Length of hospital stay Length of hospital stay (if applicable) | day 0 to 60 |
| Length of stay in ICU | day 0 to 60 |
| Duration of ventilation support / ECMO | day 0 to 60 |
| Time until negative SARS-CoV-2 PCR (nasopharyngeal sample) | time to first negative PCR will be assessed | day 0 to 60 |
| Predictive value of comorbidities | Comorbidities will be assessed and correlated to clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days) | day 0 to 60 |
| Predictive value of coagulation markers | Correlation of coagulation markers (D-Dimers, prothrombin time, Partial Thromboplastin Time, ATIII, Fibrinogen) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days) | day 0 to 60 |
| Predictive value of inflamation | Corelation of Inflammation (laboratory testing: CRP, IL-6, Ferritin, Blood cell Count) with clinical improvement (WHO scale), mortality, length of stay in ICU (days) and length of hospital stay (days) | day 0 to 60 |
| Percentage of former COVID-19 patients willing to donate qualifying for plasma donation. | through study completion, an average of 8 months |
| Amount of Plasma Units that could be collected for the clinical trial | through study completion, an average of 8 months |
| Titer of anti-SARS-CoV-2 in transfused plasma units | any plasmaphereseis, through study completion, an average of 8 months |
| Impact of donor characteristics on anti-SARS-CoV-2 humoral response | Anti-SARS-CoV-2-antibody titers will be correlated with age; gender; severity of COVID-19; interval between resolution of symptoms and plasmapheresis of plasma donors | up to 60 days |
| Course of anti-SARS-CoV-2 titer in both patient groups at different time points related to transfusion of convalescent plasma | Neutralizing anti-SARS-CoV-2 titers were measured by PRNT | up to 60 days |
| Correlation of anti-SARS-CoV-2 titer in transfused plasma units and primary and key secondary outcomes. | Correlation of antibody titers with: 1. "Survival and no longer fulfilling criteria of severe COVID-19"; 2. Change in WHO ordinal scale; 3. Time to clinical improvement; 4. Length of hospital stay; 5. Length of ICU stay; 6. Length of mechanical Ventilation or ECMO support. | day 0 to 60 |
| Effect of timing of plasma transfusions | Effect of timing of plasma transfusions on outcome: comparison of early treatment, i.e. day 1, 3 and 5 in convalescent plasma group vs. delayed treatment, i.e. day 15, 17, 19 in patients crossing over from control group due to progressive disease on day-14 assessment. | day 0 to 60 |
| Long term survival | Long term survival up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). And high-titer group versus low -titer group versus control. | 15 month |
| Frequency of long COVID-19 | Frequency of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors).And high-titer group versus low -titer group versus control. | 15 month |
| Resolution of pneumonia and functional recovery | Resolution of pneumonia and functional recovery* in patients (CCP group compared to control group and donors). Assessment will be done by CTCAE 5.0 and structured interview. And high-titer group versus low -titer group versus control. | 15 month |
| Patient Reported Outcome: FACIT Fatigue Score | FACIT Fatigue Score: 0-53 : The higher the score, the better the quality of life Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group. | 15 month |
| Patient Reported Outcome: FACIT Dyspnea Score | FACIT Dyspnea Score 1 and 2: 0-30 : The lhigher the score the worse is the dypnea Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group. | 15 month |
| Patient Reported Outcome: EQ-5D-5L visual Scale | EQ-5D-5L visual scale: 0-100, The lower the socre, the worse is the health state Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group. | 15 month |
| Patient Reported Outcome:EQ-5D-5L cross walk | EQ-5D-5L cross walk score: 0-1.0 The lower the socre, the worse is the health state Comparisons between patients CCP group compared to control group and donors and high-titer group versus low -titer group versus control group. | 15 month |
| Laboratory markers: D-Dimers | D-Dimers will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Laboratory markers: Fibrinogen | Fibronogen will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Laboratory markers: CRP | CRP will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Laboratory markers: Ferritin | Ferritin will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Laboratory markers: IL-6 | IL-6 will be correlated with the Levels of SARS-CoV-2 antodies as a measure of anti-SARS-CoV-2 immunity and compared between the patient groups (in patients: CCP group compared to control group and donors). The effect of SARS-CoV-2 vaccination* in control group, CCP group and CCP donors will also be taken into account.Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Severity of long COVID-19 | Severity of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). Grading according Post-COVID-19 Scale from 0 (no functional limitations) to 4 (severe functional limitations). Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Duration of long COVID-19 | Duration of long COVID-19* up to 15 months after randomisation (patients in CCP group* compared to control group) or first plasma donation (CCP donors). Measures will also be compeared between high-titer group versus low -titer group versus control group. | 15 month |
| Frankfurt |
| Hessia |
| 60590 |
| Germany |
| Saarland University Hospital | Homburg | Saarland | 66421 | Germany |
| University Hospital Berlin, Charite | Berlin | 13353 | Germany |
| Universitiy Hospital Dresden | Dresden | 01307 | Germany |
| University Düsseldorf | Düsseldorf | 40225 | Germany |
| University Hospital Freiburg | Freiburg im Breisgau | 79110 | Germany |
| University Hospital Gießen | Giessen | 35392 | Germany |
| University Hopsital Greifswald | Greifswald | 17487 | Germany |
| Städtisches Klinikum Karslruhe | Karlsruhe | 76133 | Germany |
| Universtity Hospital Schleswig-Holstein | Kiel | 24105 | Germany |
| Universtity Hospital Schleswig-Holstein | Lübeck | 23538 | Germany |
| University Hospital Mannheim | Mannheim | 68167 | Germany |
| University Hospital Marburg | Marburg | 35033 | Germany |
| Klinikum Stuttgart | Stuttgart | 70174 | Germany |
| University Hospital Tübingen | Tübingen | 72076 | Germany |
| Iannizzi C, Chai KL, Piechotta V, Valk SJ, Kimber C, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Jindal A, Cryns N, Estcourt LJ, Kreuzberger N, Skoetz N. Convalescent plasma for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2023 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5. |
| 36326824 | Derived | Korper S, Gruner B, Zickler D, Wiesmann T, Wuchter P, Blasczyk R, Zacharowski K, Spieth P, Tonn T, Rosenberger P, Paul G, Pilch J, Schwable J, Bakchoul T, Thiele T, Knorlein J, Dollinger MM, Krebs J, Bentz M, Corman VM, Kilalic D, Schmidtke-Schrezenmeier G, Lepper PM, Ernst L, Wulf H, Ulrich A, Weiss M, Kruse JM, Burkhardt T, Muller R, Kluter H, Schmidt M, Jahrsdorfer B, Lotfi R, Rojewski M, Appl T, Mayer B, Schnecko P, Seifried E, Schrezenmeier H. One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients. J Clin Invest. 2022 Dec 15;132(24):e163657. doi: 10.1172/JCI163657. |
| 36275695 | Derived | Korper S, Schrezenmeier EV, Rincon-Arevalo H, Gruner B, Zickler D, Weiss M, Wiesmann T, Zacharowski K, Kalbhenn J, Bentz M, Dollinger MM, Paul G, Lepper PM, Ernst L, Wulf H, Zinn S, Appl T, Jahrsdorfer B, Rojewski M, Lotfi R, Dorner T, Jungwirth B, Seifried E, Furst D, Schrezenmeier H. Cytokine levels associated with favorable clinical outcome in the CAPSID randomized trial of convalescent plasma in patients with severe COVID-19. Front Immunol. 2022 Oct 6;13:1008438. doi: 10.3389/fimmu.2022.1008438. eCollection 2022. |
| 34464358 | Derived | Korper S, Weiss M, Zickler D, Wiesmann T, Zacharowski K, Corman VM, Gruner B, Ernst L, Spieth P, Lepper PM, Bentz M, Zinn S, Paul G, Kalbhenn J, Dollinger MM, Rosenberger P, Kirschning T, Thiele T, Appl T, Mayer B, Schmidt M, Drosten C, Wulf H, Kruse JM, Jungwirth B, Seifried E, Schrezenmeier H; CAPSID Clinical Trial Group. Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19. J Clin Invest. 2021 Oct 15;131(20):e152264. doi: 10.1172/JCI152264. |
| 32738255 | Derived | Conzelmann C, Gilg A, Gross R, Schutz D, Preising N, Standker L, Jahrsdorfer B, Schrezenmeier H, Sparrer KMJ, Stamminger T, Stenger S, Munch J, Muller JA. An enzyme-based immunodetection assay to quantify SARS-CoV-2 infection. Antiviral Res. 2020 Sep;181:104882. doi: 10.1016/j.antiviral.2020.104882. Epub 2020 Jul 29. |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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