Clinical trial NCT00330148: Randomized Clinical Trial of Three Drug Combinations for Late-Stage Gambiense Human African Trypanosomiasis
Official title: Clinical Trial Comparing the Therapeutic Combinations Melarsoprol-Nifurtimox, Melarsoprol-Eflornithine and Eflornithine-Nifurtimox in the Treatment of Gambiense Human African Trypanosomiasis in the Meningo-Encephalitic Phase
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Trypanosomiasis, African
Keywords: trypanosomiasis
gambiense
combination drug therapy
sleeping sickness
Uganda
Lead sponsor: Epicentre
Sponsor class: OTHER
Collaborators: name: Médecins Sans Frontières, France
name: Embassy of France in Uganda
name: National Sleeping Sickness Control Program, Uganda
First posted: 2006-05-26
Enrollment: 435
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The treatment human African trypanosomiasis (HAT) in the meningoencephalitic phase relies on two molecules officially registered: melarsoprol, the most commonly used, has a poor safety profile and is becoming ineffective due to parasite resistance; and eflornithine, with better tolerance but more complicated and expensive to implement in endemic countries. nifurtimox, registered only for Chagas' disease but used off-label since the 1970's in series of cases of HAT, is at present the only other available alternative.

The very limited number of compounds available, the lack of prospects for the development of new products and the emergence of resistance are arguments for the use of therapeutic combinations.

This study evaluates the efficacy and safety of three drug combination therapies: melarsoprol-nifurtimox, melarsoprol-eflornithine and eflornithine-nifurtimox.

Detailed description: Dosages per drug are the same in either arm of the study: IV melarsoprol 1.8 mg/kg/day, daily for 10 days; IV eflornithine 400 mg/kg/day, 6-hourly for 7 days; oral nifurtimox 15 or 20 (children \<15 years) mg/kg/day, 8-hourly for 10 days.

For efficacy assessment, patients are followed-up for 24 months after treatment, with planned clinical and laboratory controls.

The safety assessment includes clinical and hematological adverse events.

Eligibility criteria: Inclusion Criteria:

* confirmed second-stage T.b. gambiense infection :

  * Infection diagnosed parasitologically (blood or lymph node fluid) and white blood cells \> 5/mm3 in cerebrospinal fluid (CSF)
  * or Trypanosomes detected in the CSF with any CSF cell count
* and resident in the district
* and written consent of the patient or of one of the parents/guardians for children under 15 years of age.

Exclusion Criteria:

* Trypanosome absent from blood (or lymph node fluid) and from CSF
* Or women pregnant on inclusion
* Or previous history of HAT confirmed treated during the last 24 months
* Or impossibility of regular access to the treatment centre during the 2 years following the end of the treatment
* Or less than 10 kg of body weight
* Or refugee patient

Primary outcomes:
measure: Cure rate
Secondary outcomes:
measure: Adverse events temporally associated with the treatment
measure: Major adverse events temporally associated with the treatment
Other outcomes:
Locations:
city: Omugo
country: Uganda
facility: Omugo Sleeping Sickness Treatment Center
state: Arua District
Study officials:
affiliation: Epicentre
name: Gerardo Priotto, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Legros D, Ollivier G, Gastellu-Etchegorry M, Paquet C, Burri C, Jannin J, Buscher P. Treatment of human African trypanosomiasis--present situation and needs for research and development. Lancet Infect Dis. 2002 Jul;2(7):437-40. doi: 10.1016/s1473-3099(02)00321-3.