Randomized Trial of Erythropoietin During Cerebral Malaria (EPOMAL)

June 12, 2008 updated by: Claude Bernard University

Randomized Trial of Erythropoietin to Prevent Death From Cerebral Impairment During Severe Malaria

Malaria remains one of the most common life-threatening illnesses in the tropics with a dramatic toll of more than one million deaths each year. A majority of malaria cases are non-complicated and only few evolve towards severe malaria resulting from the combination of parasite-specific virulence factors and host inflammatory responses. Cerebral malaria (CM) kills more than 1 million African children each year. CM carries a fatality rate of about 20% in adults, higher in children, despite timely and adequate chemotherapy. Moreover, the more rapid clearance of parasitaemia with new antimalarial drugs is not associated with improved survival, suggesting the potential interest for adjunctive therapies in the early phase of the disease.

Cerebral malaria leading to seizure and coma is associated with severe intracranial hypertension caused by brain-swelling. Recent imaging and post-mortem findings in adult cerebral malaria have confirmed the presence of diffuse cerebral oedema with thalamic and cerebellar white matter hypoattenuation, diffuse petechial hemorrhages and symmetric ischemic changes involving the thalamus and the cerebellum. However, the nature of the pathogenetic processes leading to cerebral malaria is incompletely understood but mechanisms linking cytokines with endothelial cells activation in the cerebral microvasculature have been recently stressed. The effect of new neuroprotective therapies has not yet been investigated, although the manifestations of cerebral malaria partly share features with neurological stroke or acute non-specific neurological disorders. The hormone erythropoietin (EPO) is probably one of the more enthusiastic drugs in this area.

EPO is as a member of type I cytokine superfamily with multiple functions, including a prominent role for erythropoiesis and neuroprotection. Systematically administered EPO crosses the blood brain barrier via the abundant expression of EPO receptors at brain capillaries, and acts as an anti-apoptotic and cytoprotective cytokine. Moreover, EPO prevents inflammation by inhibiting pro-inflammatory cytokines including TNFα, preserves endothelial cells integrity and prevents blood-brain barrier permeability. We propose a randomized clinical trial to investigate the safety and efficacy of EPO in patients presenting cerebral malaria and hospitalized at Gabriel Toure hospital, Bamako, Mali, to reduce the incidence of premature death in hospitalized patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali
        • Recruiting
        • Gabriel Toure Hospital
        • Contact:
          • Ogobara K DOUMBO, MD PhD
          • Phone Number: 223-222-8109
          • Email: okd@mrtcbko.org
        • Contact:
        • Sub-Investigator:
          • Salimata KONATE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Children between 6 months and 14 years old
  • Severe cerebral malaria due to Plasmodium falciparum
  • Coma (Blantyre score <3)
  • Enlightened assessment

Exclusion Criteria:

  • Any case of participation refusal
  • Presence of another obvious affection being able to explain the state of the patient
  • Negative malaria test (thick smear / thin smear)
  • Severe anaemia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
Patients in group I received intravenous quinine followed by oral ACT for a total period of 6 days.
Drug: Placebo
Saline Admission, day 1, day 2 3 days
Experimental: 2
Patients in group II received antimalarial drug as in group I and in addition 1500U/kg/day of rHUEPO for the initial 3 days.
Drug: Erythropoietin
Erythropoietin, 1500 U/kg/day Admission, day 1, day 2 3 days
Other Names:
  • Neorecormon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Survival
Time Frame: day 5 post-inclusion
day 5 post-inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Claude Bernard University

Investigators

  • Principal Investigator: Stephane PICOT, MD PhD, Claude Bernard University, Malaria Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Anticipated)

December 1, 2008

Study Completion (Anticipated)

March 1, 2009

Study Registration Dates

First Submitted

June 11, 2008

First Submitted That Met QC Criteria

June 12, 2008

First Posted (Estimate)

June 13, 2008

Study Record Updates

Last Update Posted (Estimate)

June 13, 2008

Last Update Submitted That Met QC Criteria

June 12, 2008

Last Verified

June 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2516114389

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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