Convalescent Plasma of Covid-19 to Treat SARS-COV-2 a Randomized Doble Blind 2 Center Trial (CPC-SARS)

Plasma From Covalescent Donors With Covid-19 for the Management of Patients With SARS-COV-2 Fase II and III, a Doble Center Randomized Doble Blind Trial

The new SARS-CoV-2 coronavirus is an emerging virus originating in Wuhan, China that has spread rapidly throughout the world. As of March 24, 2020, China had reported 81,767 cases with 3,281 deaths, and the World Health Organization (WHO) declared coronavirus 19 (COVID-19) a pandemic. COVID-19 disease is currently a pandemic without specific therapeutic agents and substantial mortality. So it is of utmost importance to find new treatments. Various therapies, such as Remdesivir and Favipiravir, are being investigated but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was used as an empirical treatment during the Ebola virus outbreaks in 2014 and in 2015 a protocol was established for the treatment of the Middle East respiratory syndrome coronavirus (MERS) with convalescent plasma. This approach with other viral infections such as SARS-CoV, H5N1 avian influenza and H1N1 influenza suggesting that plasma transfusion from convalescent donors was effective.

For this study, plasma from convalescent donors will be collected from those donors who have recovered from SARS-CoV-2 and are between 10 and 14 days after illness. Immunoassays will be carried out to detect total IgM and IgG antibodies against SARS-CoV-2. Patients will receive 1 to 3 convalescent plasma transfusions, depending on the response to treatment.

The expected results are: normal body temperature, decrease in viral load or negative between 10-12 days after transfusion of convalescent plasma, which does not progress to ARDS, extubation of mechanical ventilation within two weeks of treatment, recovery of patient.

Study Overview

• Status: Completed
• Conditions: SARS Pneumonia
• Intervention / Treatment: Biological: Convalescent Plasma of patients with COVID-19; Other: placebo (hartmann plus albumine)

Detailed Description

Currently, SARS-CoV-2 disease represents a Public Health emergency of international concern. The new coronavirus COVID-19 is estimated to have infected more than 1.8 million people worldwide. The WHO estimates that the contagion rate (R0) of the virus is 1.4 to 2.5, which affects its exponential replication. In the absence of an effective treatment for SARS-CoV-2 disease, there is an urgent need to evaluate therapeutic alternatives that reduce the mortality and morbidity of this virus. There is scientific evidence that supports the use of convalescent donor plasma for the treatment of emerging virus outbreaks and suggests that the transfusion of convalescent donor plasma is effective, and therefore the following question is established:

The use of plasma from convalescent donors by COVID-19 in patients with SARS-CoV-2 disease, stage II (moderate) and III (severe), is a treatment that reduces mortality?

Given that the mortality rate is a very relevant fact, which concerns the general population, the clinical treatments that can be used to reduce the mortality rate of critical cases are of great relevance. There are patients recovered from COVID-19 who are potential plasma donors, and in turn, many critical patients who need to receive it.

Currently, there are no effective treatments to address COVID-19 disease. A recent WHO report indicates that early results with the use of convalescent plasma suggest that it may be a potentially useful treatment modality for severe SARS-CoV-2 disease. The use of convalescent plasma from COVID-19 in acute infected patients is currently considered an experimental therapy. This implies the need to promote clinical trials in order to demonstrate their efficacy. It is recommended that the entire process from donor selection, processing, labeling, storage and distribution to be carried out in a specifically licensed institution. These institutions must have all the guarantees that prove the correct practice of the procedures.

The use of convalescent plasma has been used as rescue therapy in patients with SARS whose condition continues to deteriorate despite treatment with methylprednisolone pulses, in addition, different studies have shown a decrease in hospital stay, and lower mortality in patients treated with convalescent plasma compared to those in which this treatment was not used.

A multicenter randomized study by Hung showed that the use of convalescent plasma in patients with type A H1N1 influenza was associated with a lower viral load and a reduction in mortality 5 days after the onset of symptoms. A Mair-Jenkins meta-analysis showed that mortality was reduced after several doses of convalescent plasma, and another meta-analysis by Luke identified in 1703 patients with influenza pneumonia (1918-1925) that the use of convalescent plasma blood products an absolute reduction. 21% (95% CI 15-27; p = 0.001) in crude fatality with low risk of bias.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 04470
    • Hospital Nava de Alta Especialidad
  • Mexico City, Mexico, 06720
    • Hospital General de Mexico Dr Eduardo Liceaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults 18 to 70 years of age.
• Serious or critically ill patients confirmed for SARS-CoV-2 disease (RT-PCR).
• Meet the criteria for Disease with SARS-CoV-2 disease, phase II (Moderate) and phase III (severe) .
• Suspected Cytokine Release Syndrome with Hscore 169 points.
• Presence of severe acute hypoxemia with SpO2 <90% in ambient air and / or PaO2 / FiO2 <300 mmHg.
• Meet criteria (plain chest tomography or plain chest radiograph) for SARS-CoV-2 disease.
• Supplemental oxygen requirement either through the facial store plus reservoir bag, high-flow nasal tips or advanced airway management and invasive mechanical ventilation support.

Exclusion Criteria:

• patient has no interest in participating in the trial.
• Bilateral pulmonary infiltrate related to heart failure or other cause of water overload.
• Virus positive respiratory viral panel other than COVID-19
• History of allergy to plasma, sodium citrate, or methylene blue.
• Patients with a history of autoimmune diseases or selective IgA insufficiency.
• Those patients who are participating in other protocols.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXP-PC-F2; Patients with Pneumonia due to SARS-COV-2 phase 2 with Hyperimmune Plasma from Convalescent patients and conventional Therapy (Azithromycin and Hydroxychloroquine)	Biological: Convalescent Plasma of patients with COVID-19; Convalescent Plasma from patients with covid-19 by Apheresis, the maximum plasma volume withdrawn per session should not exceed 600 mL, excluding the anticoagulant volume, or 16% of the total blood volume, in the absence of volumetric replacement.; Other Names: Hyperinmunne plasma
Placebo Comparator: EXP-NONPC-F2; 20 Patients with Pneumonia due to SARS-COV-2 phase 2 with conventional Therapy (Azithromycin and Hydroxychloroquine) and 20% Albumin in Hartman Solution.	Other: placebo (hartmann plus albumine); use of albumin 20% in 250cc of Hartmann solution
Experimental: EXP-PC-F3; 20 Patients with Pneumonia due to SARS-VOC-2 phase 3 with Hyperimmune Plasma from Convalescent patients and conventional Therapy (Azithromycin and Hydroxychloroquine)	Biological: Convalescent Plasma of patients with COVID-19; Convalescent Plasma from patients with covid-19 by Apheresis, the maximum plasma volume withdrawn per session should not exceed 600 mL, excluding the anticoagulant volume, or 16% of the total blood volume, in the absence of volumetric replacement.; Other Names: Hyperinmunne plasma
Placebo Comparator: EXP-NONPC-F3; 20 Patients with Pneumonia due to SARS-VOC-2 phase 3 with conventional Therapy (Azithromycin and Hydroxychloroquine) and 20% Albumin in Hartman Solution.	Other: placebo (hartmann plus albumine); use of albumin 20% in 250cc of Hartmann solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death	any cause	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lenth of stay ICU	Time for discharge from the ICU	15 days
Days of Mechanical Ventilation	Number of days with ventilatory support	15 days
Suplemental Oxigen support	Number of days with need of oxigen suport without Mechanical Ventilation	15 days
Viral Load by RT-PCR	changes in viral load	15 days
Inflamatory biomarkers	changes in pro- inflamatory and anti-inflamatory biomarkes (IL-6, PCR, Ferritine, D Dimer, IL-8 IL-10	15 days
SOFA (sequencial Organ Failure Assesment)	changes in SOFA scale	15 days

Collaborators and Investigators

• Sponsor: Grupo Mexicano para el Estudio de la Medicina Intensiva
• Collaborators: Instituto Nacional de Enfermedades Respiratorias; National Institute of Pediatrics, Mexico; Hospital General Naval de Alta Especialidad - Escuela Medico Naval
• Investigators: Study Chair: ORLANDO CARILLO-TORRES, PHD, Hospital General de México Dr. Eduardo Liceaga

Publications and helpful links

General Publications

• Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
• Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27. No abstract available.
• van Griensven J, Edwards T, de Lamballerie X, Semple MG, Gallian P, Baize S, Horby PW, Raoul H, Magassouba N, Antierens A, Lomas C, Faye O, Sall AA, Fransen K, Buyze J, Ravinetto R, Tiberghien P, Claeys Y, De Crop M, Lynen L, Bah EI, Smith PG, Delamou A, De Weggheleire A, Haba N; Ebola-Tx Consortium. Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea. N Engl J Med. 2016 Jan 7;374(1):33-42. doi: 10.1056/NEJMoa1511812.
• Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis. 2011 Feb 15;52(4):447-56. doi: 10.1093/cid/ciq106. Epub 2011 Jan 19.
• Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020 Mar 16;14(1):69-71. doi: 10.5582/bst.2020.01020. Epub 2020 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2020
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): December 10, 2020

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: SARS-COV-2, CONVALESCENT PLASMA
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: DI/20/201/04/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD will be shared by petition.
• IPD Sharing Time Frame: 3 months after completion up to five years
• IPD Sharing Access Criteria: proposal should be directed to gmemiinv@gmails.com, to gain access, requestor will need to sign a data access agreement
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No