Emergency Evaluation of Convalescent Plasma for Ebola Viral Disease (EVD) in Guinea

NCT02342171 | Completed Phase 2 Results

• 1 other identifier: ITM0614
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 1

Brief Summary

This is an emergency, phase 2/3, open-label, non-randomized, clinical trial that will evaluate Convalescent Plasma (CP) added to standardized supportive care (SC) in patients with confirmed Ebola Virus Disease (EVD). No patient will be refused CP when compatible products are available and all efforts will be made to maximize CP availability during the study. EVD patients recruited during the period before CP becomes available or for whom no compatible CP is available will be given SC and will be followed for study outcomes. Data from these SC patients will be the used as comparator in the analysis of the study. The primary objective of the study is to assess if CP + SC improves the 14 day survival of patients, compared to SC alone. The Investigators aim to enroll a total number of 130 - 200 patients who will be treated treated with CP assuming equal numbers of patients treated with SC alone. If there would be insufficient patients treated with SC, patients treated at the research site prior to study start may be included in the comparison group. Patients will be recruited in the Ebola Treatment centre managed by Medecins Sans Frontieres (MSF) in Conakry, Guinea. All patients and/or relatives presenting at the centre will be informed about the study, and will be invited to provide consent at the time of admission inside the treatment centre. Only patients for whom ebola infection is confirmed with polymerase chain reaction (PCR) will be enrolled in the study. After inclusion, eligibility to the intervention will be reassessed on regular intervals. If the eligibility criteria are not met by 48 hours after inclusion, only SC will be continued. In line with the guidance of the World Health Organization (WHO), two units of CP will be given. EVD patients will be transfused with ABO-compatible CP using standard procedures. Details on the modalities of transfusion can be found in the WHO guidance document and the MSF guidelines on blood transfusion. All patients will be under close observation for transfusion-related adverse reactions during and up to 4 hours after transfusion. 24 hours after the start of transfusion, a blood sample will be collected for viral load assessment. All other aspects of patient management will be according to MSF clinical guidelines. The decision to discharge a patient should be taken on clinical grounds, but can be supported by the laboratory results. After discharge, the patient will be followed up by the study team until day 30.

Conditions

Hemorrhagic Fever, Ebola

Keywords

Ebola Viral Disease; Convalescent Plasma; Developing Countries

Outcome Measures

Primary Outcomes (1)

• Survival at Day 14 After Start of Intervention

  Effect of convalescent plasma in improving patients survival at day 14; it will be considered clinically significant if there is an absolute decrease in the case fatality rate of 20% or more, compared to SC alone

  14 days

Secondary Outcomes (9)

• Number of Participants With 30 Days Survival

  30 days

• Titer of Ebola Viral RNA

  30 days

• Titer of Ebola Viral RNA

  30 days

• Number of Participants Who Died Corresponding to EV Antibody Levels (Anti-EBOV IgG)

  14 days

• Number of Participants Who Died Corresponding to EV Antibody Levels (Neutralizing Antibodies)

  14 days

Study Arms (2)

Convalescent Plasma

EXPERIMENTAL

Convalescent Plasma: 400-500 mL from two donors (2 x 200-250 ml) and 10mL/kg for small adults and children \<45kg

Other: Convalescent Plasma

standard care

NO INTERVENTION

The control arm will consist of historical controls having being treated with standard of care

Interventions

Convalescent Plasma OTHER

Patients will be treated with plasma from recovered EVD patients.

Convalescent Plasma

Eligibility Criteria

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

You may qualify if:

• PCR-confirmed, symptomatic infection with Ebola virus
• Patient's, guardian's or representatives' willingness to provide written informed consent

You may not qualify if:

• A patient is not eligible to receive CP if they meet one of the following criteria:
• History of allergic reaction to blood or plasma products (as judged by the investigator or treating physician);
• Medical conditions in which receipt of additional fluid related to the transfusion (250-500 ml or in the case of children 10 ml/kg) may be detrimental to the patient (e.g. decompensated congestive heart failure or renal failure).
• Patients in shock unresponsive to fluid challenge
• Patients in shock with signs of multi-organ failure, defined as oliguria/anuria AND impaired consciousness AND/OR jaundice
• Condition of patient where the procedure of plasma administration carries a risk for the staff

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• National Blood Transfusion Centre (NBTC), Conakry, Guinea: collaborator
• Gamal Abdel Nasser University of Conakry: collaborator
• National Center for Training and Research of Maferinyah, Guinea: collaborator
• Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo: collaborator
• University of Oxford: collaborator
• University of Liverpool: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Aix Marseille Université: collaborator
• UBIVE, Institut Pasteur, Paris, France: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Etablissement Français du Sang: collaborator
• Belgian Red Cross: collaborator
• Institut Pasteur, Dakar, Sénégal: collaborator
• Médecins Sans Frontières, Belgium: collaborator
• World Health Organization: collaborator
• International Severe Acute Respiratory and Emerging Infection Consortium: collaborator

Study Sites (1)

Ebola Treatment Center

Donka, Guinea

Location

Related Publications (3)

• 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.

  PMID: 26735992 RESULT

• van Griensven J, Edwards T, Baize S; Ebola-Tx Consortium. Efficacy of Convalescent Plasma in Relation to Dose of Ebola Virus Antibodies. N Engl J Med. 2016 Dec 8;375(23):2307-2309. doi: 10.1056/NEJMc1609116. Epub 2016 Nov 14. No abstract available.

  PMID: 27959686 RESULT

• Edwards T, Semple MG, De Weggheleire A, Claeys Y, De Crop M, Menten J, Ravinetto R, Temmerman S, Lynen L, Bah EI, Smith PG, van Griensven J; Ebola_Tx Consortium. Design and analysis considerations in the Ebola_Tx trial evaluating convalescent plasma in the treatment of Ebola virus disease in Guinea during the 2014-2015 outbreak. Clin Trials. 2016 Feb;13(1):13-21. doi: 10.1177/1740774515621056. Epub 2016 Jan 14.

  PMID: 26768570 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Limitations and Caveats

There are clear limitations with respect to the use of a historical control group, and we cannot exclude the possibility that unmeasured confounding factors may have biased the mortality comparison.

Results Point of Contact

• Title: Prof. Dr. Johan van Griensven
• Organization: Institute of Tropical Medicine

jvangriensven@itg.be

+3232476426

Study Officials

• Johan van Griensven, MD

  ITM

  STUDY CHAIR

• Niankoye Haba, MD

  National Blood Transfusion Centre (NBTC), Conakry, Guinea

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 19, 2015
• Study Start: February 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 22, 2019
• Results First Posted: July 1, 2019

Record last verified: 2019-07

Locations

GU (1)