Clinical trial NCT00216346: Safety and Efficacy Study of Paromomycin to Treat Visceral Leishmaniasis
Official title: A Phase 3 Multicenter, Randomized, Controlled, Clinical Trial to Assess the Safety and Efficacy of Injectable Paromomycin in Patients With Visceral Leishmaniasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Visceral Leishmaniasis
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: World Health Organization
First posted: 2005-09-22
Enrollment: 667
Sex: ALL
Minimum age (years): 5
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Symptomatic Visceral Leishmaniasis(VL)is fatal; Due to the increasing resistance to standard therapy with antimonials, there is a need for new safe, efficacious, low-cost therapies for the treatment of VL. Paromomycin is an off-patent aminoglycoside antibiotic with anti-leishmaniasis activity. This study will test the safety and efficacy of paromomycin in the treatment of patients with VL in India.


Eligibility criteria: Inclusion Criteria:

* Age between 5-55 years (inclusive) of either gender.
* Newly diagnosed VL or VL treatment failure confirmed by spleen or bone marrow aspirate.
* Clinical signs and symptoms compatible with VL: fever of over two weeks duration and splenomegaly.
* Biochemical and haematological test values as follows:

  * Haemoglobin \> 5.0g/100mL
  * White blood cell count \> 1 x109/L
  * Platelet count \> 50 x 109/L
  * AST, ALT and alkaline phosphatase \< 3 times upper normal limit
  * Prothrombin time \< 5 seconds above control
  * Serum creatinine levels within normal limits
  * Serum potassium levels within normal limits
* HIV negative

Exclusion Criteria:

* A history of intercurrent or concurrent diseases (e.g. chronic alcohol consumption or drug addiction; renal, hepatic, cardiovascular or central nervous system disease; diabetes; tuberculosis or other infectious or major psychiatric diseases) that may introduce variables affecting the outcome of the study.
* Any condition which the investigator thinks may prevent the patient from completing the study therapy and subsequent follow-up.
* An abnormal baseline audiogram (presentation with 75 dB or higher at 8KHz or below) and/or a history of significant vestibular or auditory dysfunction.
* Proteinuria (\> 2+).
* A history of allergy or hypersensitivity to aminoglycosides.
* A history of major surgery within the last two weeks.
* Pregnancy or lactation. \[Note: women of childbearing age must use an adequate form of contraception (documented) or agree to a period of sexual abstinence during the treatment phase of the study.\]
* Previous treatment for VL within two weeks of enrolment into the study.
* Prior treatment failures with paromomycin or amphotericin B.

Primary outcomes:
measure: (1) To compare the safety of injectable paromomycin to amphotericin B when administered in the proposed dosage regimens.
measure: (2) To compare the efficacy of injectable paromomycin to amphotericin B with regards to final cure rates.
Secondary outcomes:
measure: - Characterization of the pharmacokinetics of injectable paromomycin in adults and children with VL
measure: - Comparison of initial cure rates for the two regimens
measure: - Comparison of clinical improvement rates for the two regimens
Other outcomes:
Locations:
city: Agam Kuan, Patna
country: India
facility: Rajendra Memorial Research Institute of Medical Sciences (ICMR)
state: Bihar
city: Brahmpura, Muzaffarpur
country: India
facility: Kalazar Research Centre
state: Bihar
city: Patna
country: India
facility: Kalazar Research Centre
state: Bihar
city: Rambagh Road Muzaffarpur
country: India
facility: Kala-azar Medical Research Centre
state: Bihar
Study officials:
affiliation: Kala-azar Research Centre
name: Prof S. Sundar
role: PRINCIPAL_INVESTIGATOR
affiliation: Kalazar Research Centre
name: Prof T.K. Jha
role: PRINCIPAL_INVESTIGATOR
affiliation: Kalazar Research Centre
name: Prof C.P. Thakur
role: PRINCIPAL_INVESTIGATOR
affiliation: Rajendra Memorial Research Institute of Medical Sciences (ICMR)
name: Dr. S.K. Bhattacharya
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med. 2007 Jun 21;356(25):2571-81. doi: 10.1056/NEJMoa066536.