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Randomized Trial of Erythropoietin During Cerebral Malaria (EPOMAL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by Claude Bernard University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Claude Bernard University
ClinicalTrials.gov Identifier:
NCT00697164
First received: June 11, 2008
Last updated: June 12, 2008
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Cerebral Malaria
Drug: Placebo
Drug: Erythropoietin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Trial of Erythropoietin to Prevent Death From Cerebral Impairment During Severe Malaria

Resource links provided by NLM:


Further study details as provided by Claude Bernard University:

Primary Outcome Measures:
  • Survival [ Time Frame: day 5 post-inclusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: October 2007
Estimated Study Completion Date: March 2009
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Neorecormon

  Eligibility

Ages Eligible for Study:   6 Months to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697164

Contacts
Contact: Stephane PICOT, MD PhD 33-4-7877-7502 stephane.picot@sante.univ-lyon1.fr
Contact: Anne-Lise BIENVENU, PharmD PhD 33-4-7877-7591 anne-lise.bienvenu@recherche.univ-lyon1.fr

Locations
Mali
Gabriel Toure Hospital Recruiting
Bamako, Mali
Contact: Ogobara K DOUMBO, MD PhD    223-222-8109    okd@mrtcbko.org   
Contact: Salimata KONATE, MD    223-222-8109    salimata57@yahoo.fr   
Sub-Investigator: Salimata KONATE, MD         
Sponsors and Collaborators
Claude Bernard University
Investigators
Principal Investigator: Stephane PICOT, MD PhD Claude Bernard University, Malaria Research Unit
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: PICOT/MD PhD, Claude Bernard University, Malaria Research Unit
ClinicalTrials.gov Identifier: NCT00697164     History of Changes
Other Study ID Numbers: 2516114389
Study First Received: June 11, 2008
Last Updated: June 12, 2008
Health Authority: Mali: Ministry of Health

Keywords provided by Claude Bernard University:
Malaria
Treatment
Adjunctive
Erythropoietin
Survival

Additional relevant MeSH terms:
Malaria
Malaria, Cerebral
Central Nervous System Diseases
Central Nervous System Infections
Central Nervous System Parasitic Infections
Central Nervous System Protozoal Infections
Malaria, Falciparum
Nervous System Diseases
Parasitic Diseases
Protozoan Infections
Epoetin alfa
Hematinics
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014