Anti-MERS-CoV Convalescent Plasma Therapy

Anti-MERS-COV Convalescent Plasma Therapy

Since the first report of the Middle East Respiratory Syndrome Corona virus (MERS- CoV) in September 2012, more than 800 cases have been reported to the World Health Organization (WHO) with substantial mortality.

Study Overview

• Status: Withdrawn
• Conditions: Respiratory Distress Syndrome (& [Hyaline Membrane Disease])
• Intervention / Treatment: Biological: Convalescent plasma

Detailed Description

World knowledge about this virus is accumulating but data about the clinical presentations of infected patients and common treatments, including ribavirin, interferon and methylprednisolone, lack evidence. Although drugs with anti- coronavirus (CoV) activities have been identified, as yet no anti- MERs- CoV drug has been approved and a vaccine has yet to be developed. Previous reports on other viral infections including SARS have suggested that convalescent plasma or serum is effective where no other treatment is available or in an emergency. A recently completed systematic review and meta-analysis by the University of Nottingham - World Health Organization Collaborating Center indicates that convalescent plasma therapy may be the most promising near-term therapy patients with for MERS- CoV infection. In this study, investigators will study the pharmacokinetics of immunoglobulin in response to convalescent plasma administration in order to inform a much larger study which will investigate the efficacy of convalescent plasma. Plasma will be collected from patients who recently recovered from MERS-CoV, Health Care Workers who had potential exposure and are tested for anti MERS-CoV serology and RT-PCR after obtaining their consent. This convalescent plasma will be stored in the blood bank as per their policies and procedures. Patients with MERS-CoV positive after meeting the eligibility criteria will receive 2 units of convalescent plasma . Clinical data as well as the standard laboratory studies will be collected at baseline, 30 mins after first dose, 30 mins after second dose, day 1, 3, 7, 14, 28 of hospital stay after enrollment.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh,, Saudi Arabia, 11426
    • Intensive Care Unit, King Abdulaziz Medical City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than or equal to 14 years of age
• Inpatients who are MERS-COV positive (by PCR)
• Willingness to have blood, respiratory and urine samples obtained and stored for subsequent analysis.

Exclusion Criteria:

• Clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily not MERS-CoV in origin.
• History of allergic reaction to blood or plasma products (as judged by the investigator)
• Known IgA deficiency
• Medical conditions in which receipt of 500mL volume may be detrimental to the patient (e.g., decompensated congestive heart failure)
• Females who are pregnant or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Convalescent plasma; Enrolled patients will receive 2 units of the convalescent plasma after meeting the eligibility criteria	Biological: Convalescent plasma; Convalescent plasma from patients who recently recovered from MERS-CoV, HCWs who had potential exposure and subjects who are willing to donate plasma and have their blood tested for anti MERS-CoV serology and RT-PCR after obtaining their consent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital mortality	Hospital mortality will be death in the ICU during the same hospital admission	Death in the Hospital (ICU or ward) before or at 6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU mortality	Death in the ICU during the same hospital admission.	Death in the ICU at or after 90 days of enrollment
ICU Length of Stay	Number of calendar days between admission and final discharge from ICU.	Number of days in ICU with an average expected duration of 10 days.
Duration of Mechanical Ventilation	Number of calendar days between start and final liberation from mechanical ventilation.	Number of days of mechanical ventilation with an expected average duration of 8 days
Viral load in tracheal aspirate	viral clearance from all sampled sites by day 3 after administration of CP	Serial levels in the first 28 days of enrollment
Inflammatory markers,	Epidermal Growth Factor (EGF), Eotaxin, Granulocyte colony-stimulating factor (G-CSF), Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Interferon(IFN)-γ, IFN-a2, Interleukin (IL)-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IL-17, IL-1ra, IL-1a, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, Interferon gamma-induced protein (IP)-10, Monocyte Chemotactic Protein (MCP)-1, Macrophage Inflammatory Protein (MIP)-1a, MIP-1β, Tumor Necrosis Factor-α (TNF-a), TNF-β, Vascular Endothelial Growth Factor (VEGF)	Serial levels in the first 28 days of enrollment
Anti-MERS-CoV antibodies	anti-MERS-CoV antibody level before and after administration of CP.	Serial levels in the first 28 days of enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chest X ray	X ray changes at day 0, 1, 3, 7, 14, 21 and 28	Serial changes in the X ray till day 28

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center
• Investigators: Principal Investigator: Yaseen M Arabi, MD, King Abdullah International Medical Research Center

Publications and helpful links

General Publications

• Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: July 13, 2014
• First Posted (Estimate): July 15, 2014

Study Record Updates

• Last Update Posted (Actual): November 21, 2018
• Last Update Submitted That Met QC Criteria: November 19, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Convalescent plasma; Corona Virus; Serology
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease
• Other Study ID Numbers: RC13-244