Clinical trial NCT00697164: Randomized Trial of Erythropoietin During Cerebral Malaria
Official title: Randomized Trial of Erythropoietin to Prevent Death From Cerebral Impairment During Severe Malaria
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Cerebral Malaria
Keywords: Malaria
Treatment
Adjunctive
Erythropoietin
Survival
Lead sponsor: Claude Bernard University
Sponsor class: OTHER
First posted: 2008-06-13
Enrollment: 120
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: day 5 post-inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Gabriel Toure Hospital
Study officials:
affiliation: Claude Bernard University, Malaria Research Unit
name: Stephane PICOT, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.