Inactivated Convalescent Plasma as a Therapeutic Alternative in Patients CoViD-19

Inactivated Convalescent Plasma as a Therapeutic Alternative in Hospitalized Patients CoViD-19

Convalescent plasma is a way to provide passive immunity to a person exposed to an infectious agent. It has been used as a therapeutic tool for emerging viral infections without specific treatment and with high morbidity and mortality, such as Influenza H1N1, H5N1, H7N9, Ebola, MERS, SARS-CoV1, and even SARS-Cov2, with satisfactory results regarding evolution clinic of patients treated and without significant adverse events reported. One of its main advantages of convalescent plasma is to generate a rapid immune response (even faster than a vaccine), against a pathogen that circulates in a specific geographic area, probably common for both donor and recipient.

Study Overview

• Status: Unknown
• Conditions: Infections, Coronavirus
• Intervention / Treatment: Drug: Inactivated convalescent plasma; Drug: Support treatment

Detailed Description

This study consists of obtaining convalescent plasma by means of apheresis, from recovered donors, who meet the eligibility criteria to donate. Then this plasma will be inactivated by riboflavin and UV based photochemical treatment (Mirasol technology - Terumo BCT®), in order to add more transfusion security to the procedure. Finally, it will be transfused to CoViD-19 patients hospitalized in any of the participating clinics. There are currently no reported significant adverse events associated with this therapy. Have been published two serial cases reports,more evidence is necessary to standardize the treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • Bogotá, Colombia
    • Clínica Corpas
  • Facatativa, Colombia
    • E.S.E Hospital San Rafael Facatativa
  • Popayán, Colombia
    • Clínica la Estancia
  • Antioquía
    • Medellín, Antioquía, Colombia, 0500
      • Clínica Antioquía
    • Medellín, Antioquía, Colombia, 0500
      • Clínica Sagrado Corazón
    • Medellín, Antioquía, Colombia, 0500
      • IPS Universitaria
    • Medellín, Antioquía, Colombia, 0500
      • Universidad de Antioquia
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 1101
      • National Blood Center Foundation, Hemolife/Fundación Banco Nacional de Sangre Hemolife
  • Risaralda
    • Pereira, Risaralda, Colombia
      • Clínica Rosales
  • Valle
    • Cali, Valle, Colombia
      • Clinica Nuestra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Over 18 years old
• Confirmed laboratory diagnosis for qRT-PCR to SARS-CoV-2
• Meet any of the following medical criteria (Defined by WHO): Be currently hospitalized with: Pneumonia, Severe pneumonia, Acute Respiratory Distress Syndrome (moderate or severe), Sepsis or Septic shock
• The patient, or his representative, must sign an informed consent

Exclusion Criteria:

• Participate in another clinical trial for CoViD- 19
• History of acute allergic transfusion reactions due to transfusion of blood or other components, especially plasma components (fresh frozen plasma, cryoprecipitate and platelets),
• History of allergic reaction due to IgA deficiency
• Allergic reaction to sodium citrate or riboflavin (vitamin B2)
• History of immunosuppression

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Convalescent plasma+Support treatment selected by the hospital; Participants will receive two doses of ABO - Rh compatible inactivated convalescent plasma, each one of 200 mililiters (mL), with a 24-hour interval via transfusion, for a final volume of 400 mL, meanwhile they continue to receive the supportive treatment chosen by the hospitals, according to each institutional protocol.	Drug: Inactivated convalescent plasma; Day 0: Transfusion of 200mL of ABO -Rh compatible inactivated convalescent plasma, Start of support treatment selected by medical staff according to each institutional protocol Day 1: Transfusion of 200mL of ABO -Rh compatible inactivated convalescent plasma; Other Names: Inactivated convalescent plasma SARS-Cov-2 + Support treatment; Drug: Support treatment; Day 0: Start of support treatment selected by medical staff according to each each institutional protocol; Other Names: Support treatment under medical decision
Active Comparator: Support treatment selected by the hospital; The best support treatment selected by the hospital, according to each institutional protocol. Due to the ongoing development of knowledge of pathophysiology and scientific evidence of the available alternatives, it will be selected at the time of treatment.	Drug: Support treatment; Day 0: Start of support treatment selected by medical staff according to each each institutional protocol; Other Names: Support treatment under medical decision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality reduction in CoViD-19 patients treated with inactivated convalescent plasma + support treatment	To assess the efficacy in reducing mortality in CoViD-19 patients treated with inactivated convalescent plasma together with the support treatment selected by the respective hospital	Over a period of 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical evolution	Number of Participants with resolution of fever (<38ºC temperature)	Over a period of 28 days
Clinical evolution by seven-parameter ordinal scale	The clinical improvement will be established with a two-point improvement within this seven categories (recommended by World Organization Health-WHO): 1) Not hospitalized, with resumption of normal activities 2) Not hospitalized, but unable to resume normal activities 3) Hospitalized that does not require supplemental oxygen 4) Hospitalized requiring supplemental oxygen 5) Hospitalized requiring high-flow nasal oxygen therapy, non-invasive mechanical ventilation, or both 6) Hospitalized requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both 7) death	3, 7, 14 and 28 days
Multi-organ failure progression	Evolution by SOFA (Sequential Organ Failure Assessment), The range is between 0 and 24 points, with the highest scores being indicators of a more serious illness	3, 7, 14 and 28 days
Change in hemoglobin concentration	Compare the change in hemoglobin concentration at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in blood cell count	Compare the change in blood cell count at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in serum creatinine level	Compare the change in Serum creatinine concentration at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in aspartate aminotransferase level	Compare the change in aspartate aminotransferase level at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in alanin aminotransferase level	Compare the change in Alanine aminotransferase levels at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in bilirubin level	Compare the change in bilirubin levels at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in lactate dehydrogenase level	Compare the change in lactate dehydrogenase levels at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in creatine kinase level	Compare the change in creatine kinase levels at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in creatine kinase MB level	Compare the change in creatine kinase MB levels at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in C reactive protein concentration	Compare the change in C reactive protein concentration at 3, 7, 14 and 28 days after treatment, in mg/L	3, 7, 14 and 28 days
Change in D Dimer concentration	Compare the change in D Dimer concentration at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in Procalcitonin concentration	Compare the change in procalcitonin concentration at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Change in IL6 level	Compare the change in IL6 level at 3, 7, 14 and 28 days after treatment	3, 7, 14 and 28 days
Radiography imaging	Resolution of chest radiography imaging findings (example, bilateral, peripheral and basal predominant ground-glass opacity, consolidation, or both)	Over a period of 60 days
Tomography imaging	Resolution of tomography imaging (example, patches located in the subpleural regions of the lung)	Over a period of 60 days
Assessment of oxygenation	Arterial oxygen partial pressure (PaO2) in mmHg / Inspired fraction of oxygen (FIO2) ratio	3, 7, 14 and 28 days
Viral Load	Viral Load Quantification	0, 3, 7 days and until hospital discharge or a maximum of 60 days whichever comes first
Antibody titer	Neutralizing antibody anti SARS-CoV-2 titer evolution	Day 0, Day 3 and Day 7
Oxygen-free days through Day 60	Number of days without use of Oxygen	Until hospital discharge or a maximum of 60 days whichever comes first
Mechanical ventilation-free days through Day 28	Number of days without use of mechanical ventilation	Until hospital discharge or a maximum of 28 days whichever comes first
Intensive Care Unit (ICU)-free days through Day 28	Time outside of ICU, in days	Until hospital discharge or a maximum of 28 days whichever comes first
Hospital-free days through Day 60	Time outside of the hospital, in days	Until hospital discharge or a maximum of 60 days whichever comes first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Occurrence of adverse events during inactivated convalescent plasma transfusion, classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0	Up to 28 days

Collaborators and Investigators

• Sponsor: National Blood Center Foundation, Hemolife
• Investigators: Principal Investigator: Andrés F Zuluaga, MD, MSc, MeH, Universidad de Antioquia

Publications and helpful links

General Publications

• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
• Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003. No abstract available.
• Epstein J, Burnouf T. Points to consider in the preparation and transfusion of COVID-19 convalescent plasma. Vox Sang. 2020 Aug;115(6):485-487. doi: 10.1111/vox.12939. Epub 2020 May 14. No abstract available.

Helpful Links

• Regulatory considerations for the use of convalescent plasma to CoViD-19 emergency

Study record dates

Study Major Dates

• Study Start (Anticipated): June 20, 2020
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 30, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Apheresis; Convalescent plasma; Pathogen inactivation; CoViD-19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: CT01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No