A Clinical Trial of Convalescent Plasma Compared to Best Supportive Care for Treatment of Patients With Severe COVID-19

NCT04433910 | Completed Phase 2

• 2 other identifiers: CAPSID2020-DRK-BSD2020-001310-38
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

COVID-19

Keywords

convalescent plasma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (31)

• Time to clinical improvement

  day 0 to discharge within a 60 day period

• Frequency and severity of adverse events by CTCAE v5.0, (Key secondary endpoint)

  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

Study Arms (2)

Convalescent plasma

EXPERIMENTAL

Convalescent plasma transfusion on day 1, 3 and 5.

Drug: Convalesscent Plasma

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.

Interventions

Convalesscent Plasma DRUG

Transfusion

Convalescent plasma

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• respiratory rate ≥ 30 breaths / minute under ambient air
• requirement of any type of ventilation support
• needs ICU treatment
• Written informed consent by patient or legally authorized representative

You may not qualify if:

• 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 ventilation support
• Not considered eligible for extracorporeal oxygenation support (even in case of severe ARDS according to Berlin classification with Horovitz-Index \< 100 mg Hg)
• Chronic obstructive lung disease (COPD), stage 4
• Lung fibrosis with UIP pattern in CT und 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 \> 5xULN and elevation of ALT /AST (at least one \>10xULN).
• Any history of adverse reactions to plasma proteins
• Known deficiency of immunoglobulin A
• Pregnancy
• Breastfeeding women

Sponsors & Collaborators

• Deutsches Rotes Kreuz DRK-Blutspendedienst Baden-Wurttemberg-Hessen: lead

Study Sites (16)

University Hospital Ulm

Ulm, Baden-Württmberg, 89081, Germany

Location

University Hopsital Frankfurt

Frankfurt, Hessia, 60590, Germany

Location

Saarland University Hospital

Homburg, Saarland, 66421, Germany

Location

University Hospital Berlin, Charite

Berlin, 13353, Germany

Location

Universitiy Hospital Dresden

Dresden, 01307, Germany

Location

University Düsseldorf

Düsseldorf, 40225, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79110, Germany

Location

University Hospital Gießen

Giessen, 35392, Germany

Location

University Hopsital Greifswald

Greifswald, 17487, Germany

Location

Städtisches Klinikum Karslruhe

Karlsruhe, 76133, Germany

Location

Universtity Hospital Schleswig-Holstein

Kiel, 24105, Germany

Location

Universtity Hospital Schleswig-Holstein

Lübeck, 23538, Germany

Location

University Hospital Mannheim

Mannheim, 68167, Germany

Location

University Hospital Marburg

Marburg, 35033, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

University Hospital Tübingen

Tübingen, 72076, Germany

Location

Related Publications (6)

• 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.

  PMID: 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 Feb 1;2(2):CD013600. doi: 10.1002/14651858.CD013600.pub5.

  PMID: 36734509 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.

  PMID: 36326824 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.

  PMID: 36275695 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.

  PMID: 34464358 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.

  PMID: 32738255 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hubert Schrezenmeier, Prof.Dr.

  IKT Ulm

  PRINCIPAL INVESTIGATOR

• Erhard Seifried, Prof.Dr.Dr.

  German Red Cross Blood Service

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: June 16, 2020
• Study Start: August 30, 2020
• Primary Completion: January 21, 2021
• Study Completion: March 25, 2022
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (16)