Convalescent Plasma vs Human Immunoglobulin to Treat COVID-19 Pneumonia

NCT04381858 | Completed Phase 3 DMC

• 1 other identifier: 2020-A-10
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (5)

• Mean hospitalization time

  Mean days from admission as a suspected case of COVID with hospitalization criteria until discharge

  Through study completion, an average of 3 months

• Mean Oxigenation index evolution

  Mean of delta of oxigenation index (PaO2/FiO2)

  Through study completion, an average of 3 months

• Rate of severe ARDS

  Rate of patients with evolution to severe ARDS (PaO2/FiO2 \< 100)

  Through study completion, an average of 3 months

• Rate and time to dead

  Rate of Dead caused by COVID-19 related complications and time to dead caused by COVID-19 complication

  Through study completion, an average of 3 months

• Mean time with invasive mechanical ventilation

  Mean time with invasive mechanical ventilation

  Through study completion, an average of 3 months

Secondary Outcomes (1)

• Time to Viral PCR Negativization

  Through study completion, an average of 3 months.

Study Arms (2)

Severe pneumonia due to COVID-19

EXPERIMENTAL

Patients who are admitted to Hospital Centers with a positive RT-qPCR SARS-CoV-2 test or a CT scan compatible with a diagnosis of COVID-19 pneumonia, in addition to one of the following two criteria: 1. Severe respiratory failure \[respiratory rate\> 25 - \<35 x minute, oxygen saturation ≤ 90% with reservoir mask (FiO2 = 100%)\] 2. Requiring invasive mechanical ventilation.

Drug: Plasma from COVID-19 convalescent patient

Severe pnemonia due to COVID-19

ACTIVE COMPARATOR

Patients who are admitted to Hospital Centers with a positive RT-qPCR SARS-CoV-2 test or a CT scan compatible with a diagnosis of COVID-19 pneumonia, in addition to one of the following two criteria: 1. Severe respiratory failure \[respiratory rate\> 25 - \<35 x minute, oxygen saturation ≤ 90% with reservoir mask (FiO2 = 100%)\] 2. Requiring invasive mechanical ventilation.

Drug: Human immunoglobulin

Interventions

Plasma from COVID-19 convalescent patient DRUG

Infusion of 400 ml (2 units) of plasma. Plasma donated from convalescent patients will be extracted in strict compliance with the following criteria: * History of a clinical event with symptoms attributed to COVID-19 and a positive PCR test for COVID-19 * Further confirmation of a negative PCR test for COVID-19 * In order to be eligible plasma donors must complete at least 14 days after the last negative PCR in the absence of any symptom attributable to COVID-19 infection * IgG antibodies for COVID-19 must be confirmed POSITIVE when a qualitative assay is being used * When quantification of IgG antibodies for COVID-19 is available a title \> 1: 640 will be required for inclusion. * Apheresis will be used as the only method for plasma extraction.

Severe pneumonia due to COVID-19

Human immunoglobulin DRUG

Human immunoglobulin 0.3 gr/kg/day (5 doses)

Severe pnemonia due to COVID-19

Eligibility Criteria

• Age: 16 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are admitted to Hospital Centers with a positive RT-qPCR SARS-CoV-2 test or a CT scan compatible with a diagnosis of COVID-19 pneumonia, in addition to one of the following two criteria:
• Severe respiratory failure \[respiratory rate\> 25 - \<35 x minute, oxygen saturation ≤ 90% with reservoir mask (FiO2 = 100%)\]
• Requiring invasive mechanical ventilation.

You may not qualify if:

• Patients with a viral infection other than COVID-19

Sponsors & Collaborators

• Centenario Hospital Miguel Hidalgo: lead

Study Sites (1)

Centenario Hospital Miguel Hidalgo

Aguascalientes, 20259, Mexico

Location

Related Publications (24)

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• 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

• Piechotta V, Iannizzi C, Chai KL, Valk SJ, Kimber C, Dorando E, Monsef I, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 20;5(5):CD013600. doi: 10.1002/14651858.CD013600.pub4.

  PMID: 34013969 DERIVED

Related Links

• Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus 2019 (n-CoV) on 30 January 2020.
• World Health Organization.Coronavirus disease (COVID-19) outbreak
• The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study
• Registration format of research protocols related to the therapeutic use of plasma from convalescent donors of COVID-19 secondary to infection by SARS-CoV-2 - CNTS. National Center for Blood Transfusion

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 11, 2020
• Study Start: May 6, 2020
• Primary Completion: November 26, 2020
• Study Completion: November 26, 2020
• Last Updated: November 30, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)