Randomized Trial of Erythropoietin During Cerebral Malaria

NCT ID: NCT00697164

Last Updated: 2008-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2009-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Cerebral Malaria

Keywords

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Malaria Treatment Adjunctive Erythropoietin Survival

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Patients in group I received intravenous quinine followed by oral ACT for a total period of 6 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Saline Admission, day 1, day 2 3 days

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.

Group Type EXPERIMENTAL

Erythropoietin

Intervention Type DRUG

Erythropoietin, 1500 U/kg/day Admission, day 1, day 2 3 days

Interventions

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Placebo

Saline Admission, day 1, day 2 3 days

Intervention Type DRUG

Erythropoietin

Erythropoietin, 1500 U/kg/day Admission, day 1, day 2 3 days

Intervention Type DRUG

Other Intervention Names

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Neorecormon

Eligibility Criteria

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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
Minimum Eligible Age

6 Months

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Claude Bernard University

OTHER

Sponsor Role lead

Responsible Party

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Claude Bernard University, Malaria Research Unit

Principal Investigators

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Stephane PICOT, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Claude Bernard University, Malaria Research Unit

Locations

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Gabriel Toure Hospital

Bamako, , Mali

Site Status RECRUITING

Countries

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Mali

Central Contacts

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Stephane PICOT, MD PhD

Role: CONTACT

Phone: 33-4-7877-7502

Email: [email protected]

Anne-Lise BIENVENU, PharmD PhD

Role: CONTACT

Phone: 33-4-7877-7591

Email: [email protected]

Facility Contacts

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Ogobara K DOUMBO, MD PhD

Role: primary

Salimata KONATE, MD

Role: backup

References

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Bienvenu AL, Ferrandiz J, Kaiser K, Latour C, Picot S. Artesunate-erythropoietin combination for murine cerebral malaria treatment. Acta Trop. 2008 May;106(2):104-8. doi: 10.1016/j.actatropica.2008.02.001. Epub 2008 Feb 15.

Reference Type BACKGROUND
PMID: 18359468 (View on PubMed)

Picot S, Bienvenu AL, Konate S, Sissoko S, Barry A, Diarra E, Bamba K, Djimde A, Doumbo OK. Safety of epoietin beta-quinine drug combination in children with cerebral malaria in Mali. Malar J. 2009 Jul 24;8:169. doi: 10.1186/1475-2875-8-169.

Reference Type DERIVED
PMID: 19630971 (View on PubMed)

Other Identifiers

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2516114389

Identifier Type: -

Identifier Source: org_study_id