Randomized Trial of Erythropoietin During Cerebral Malaria

Cerebral Malaria Clinical Trial

— EPOMAL  

Official title:

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT00697164
• Other study ID #: 2516114389
• Status: Unknown status
• Phase: Phase 2/Phase 3
• First received: June 11, 2008
• Last updated: June 12, 2008
• Start date: October 2007
• Est. completion date: March 2009

Study information

• Verified date: June 2008
• Source: Claude Bernard University
• Contact: Stephane PICOT, MD PhD
• Phone: 33-4-7877-7502
• Email: stephane.picot[@]sante.univ-lyon1.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 120
• Est. completion date: March 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Malaria
• Malaria
• Malaria, Cerebral

Intervention

Drug:
• Placebo
Saline Admission, day 1, day 2 3 days
• Erythropoietin
Erythropoietin, 1500 U/kg/day Admission, day 1, day 2 3 days

Locations

Country	Name	City	State
Mali	Gabriel Toure Hospital	Bamako

Sponsors (1)

Lead Sponsor	Collaborator
Claude Bernard University

Country where clinical trial is conducted

Mali, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		day 5 post-inclusion