Randomized Trial of Erythropoietin During Cerebral Malaria

NCT00697164 | Unknown Phase 2 DMC

• 1 other identifier: 2516114389
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Malaria

Keywords

Malaria; Treatment; Adjunctive; Erythropoietin; Survival

Outcome Measures

Primary Outcomes (1)

• Survival

  day 5 post-inclusion

Study Arms (2)

1

PLACEBO COMPARATOR

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

Drug: Placebo

2

EXPERIMENTAL

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

Interventions

Placebo DRUG

Saline Admission, day 1, day 2 3 days

1

Erythropoietin DRUG

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

Also known as: Neorecormon

2

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Claude Bernard University: lead

Study Sites (1)

Gabriel Toure Hospital

Bamako, Mali

RECRUITING

Related Publications (2)

• 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.

  PMID: 18359468 BACKGROUND

• 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.

  PMID: 19630971 DERIVED

MeSH Terms

Conditions

Malaria, Cerebral; Malaria

Interventions

Erythropoietin; epoetin beta

Condition Hierarchy (Ancestors)

Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Central Nervous System Infections; Infections; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Stephane PICOT, MD PhD

  Claude Bernard University, Malaria Research Unit

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephane PICOT, MD PhD

CONTACT

33-4-7877-7502; stephane.picot@sante.univ-lyon1.fr

Anne-Lise BIENVENU, PharmD PhD

CONTACT

33-4-7877-7591; anne-lise.bienvenu@recherche.univ-lyon1.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 13, 2008
• Study Start: October 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: March 1, 2009
• Last Updated: June 13, 2008

Record last verified: 2008-06

Locations

MA (1)