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

NCT ID: NCT02342171

Last Updated: 2019-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 606 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-07-31

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.

Detailed Description

West-Africa is being ravaged by the worst outbreak of Ebola Viral Disease (EVD) ever witnessed. Nine months after its onset, the outbreak has spiraled and currently appears to be out of control. One of the key factors contributing to the high mortality is the lack of any proven effective EVD specific treatment. The identification of effective therapies is a medical and public health priority. Convalescent whole blood (CWB) and convalescent plasma (CP) have been prioritized by the World Health Organization (WHO) to be evaluated within a short time span, so that widespread use for therapy could be implemented rapidly if proven effective. Both CWB and CP contain EBV antibodies and either could potentially be of value as EVD therapy, however their efficacy in Ebola must still be demonstrated. .

This is an emergency, phase 2/3, open-label, non-randomized, clinical trial that will evaluate CP added to standardized supportive care (SC) in patients with confirmed 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. Secondary objectives are;

• to assess 30 day survival on CP + SC
• to assess the relationship between EV antibody levels in donated CP and survival in patients receiving CP
• to assess the relationship between EV antibody levels in donated CP and changes in levels of viral RNA in the blood of patients receiving CP
• to assess the occurrence of serious adverse reactions (SARs) related to CP transfusion in Ebola patients
• to assess the occurrence of safety risks related to CP transfusion in health workers administering the treatments
• to determine risk factors for mortality despite administration of CP (for identification of patients most likely to benefit)

The Investigators aim to enroll a total number of 130 - 200 patients treated with CP assuming equal numbers of patients treated with SC alone. The number of patients treated with SC will be determined by the time interval for CP to become available for treatment and the availability of CP throughout the study. 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. 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 via polymerase chain reaction (PCR) will be enrolled in the study. After inclusion, eligibility to the intervention will be assessed at the time of enrollment (when the patient is moved to the area for patients with confirmed Ebola) and will be reassessed on regular intervals as long as the patient did not receive plasma transfusion. The re-assessment of eligibility to receive CP happens at 8h and at 12h, and is repeated until 48 hours after inclusion. If the eligibility criteria are not met by 48 hours after inclusion, only SC will be continued.

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); (this first criterion is definite and will not be re-assessed)
• 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

In line with the WHO guidance, 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Convalescent Plasma

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

Group Type: EXPERIMENTAL

Convalescent Plasma

Intervention Type: OTHER

Patients will be treated with plasma from recovered EVD patients.

standard care

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Convalescent Plasma

Patients will be treated with plasma from recovered EVD patients.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Blood Transfusion Centre (NBTC), Conakry, Guinea

UNKNOWN

Sponsor Role: collaborator

Gamal Abdel Nasser University of Conakry

OTHER

Sponsor Role: collaborator

National Center for Training and Research of Maferinyah, Guinea

UNKNOWN

Sponsor Role: collaborator

Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

University of Liverpool

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: collaborator

Aix Marseille Université

OTHER

Sponsor Role: collaborator

UBIVE, Institut Pasteur, Paris, France

UNKNOWN

Sponsor Role: collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

Etablissement Français du Sang

OTHER

Sponsor Role: collaborator

Belgian Red Cross

OTHER

Sponsor Role: collaborator

Institut Pasteur, Dakar, Sénégal

UNKNOWN

Sponsor Role: collaborator

Médecins Sans Frontières, Belgium

OTHER

Sponsor Role: collaborator

World Health Organization

OTHER

Sponsor Role: collaborator

International Severe Acute Respiratory and Emerging Infection Consortium

OTHER

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johan van Griensven, MD

Role: STUDY_CHAIR

ITM

Niankoye Haba, MD

Role: PRINCIPAL_INVESTIGATOR

National Blood Transfusion Centre (NBTC), Conakry, Guinea

Locations

Ebola Treatment Center

Donka, , Guinea

Countries

Guinea

References

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.

Reference Type: RESULT

PMID: 26735992 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27959686 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26768570 (View on PubMed)

Other Identifiers

ITM0614

Identifier Type: -

Identifier Source: org_study_id