The disease leishmaniasis, caused by protozoan Leishmania parasites and transmitted via infected female sandflies and reservoir hosts is endemic in 88 countries and 350 million people are at risk. Leishmaniasis prevalence is >12 million cases/year and the incidence is >2.5 million cases/year. The estimated disease burden is 2.4 million DALYs. Leishmaniasis is a category 1 disease (Emerging or uncontrolled diseases) and the World Health Organization (WHO) has acknowledged it as a severely neglect
Conditions
Interventions
In this project, Pentamidine Isethionate treatment will be studied in a randomized controlled trial with 2 treatment arms:
1. 4mg/kg body weight im. at day 1, 4 and 7 (control / usual care arm) or
Sponsors
Koninklijk Instituut voor de Tropen (KIT)
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patient is 16 years and older of age; 2. Histopathology and/or smear of skin biopsy confirms diagnosis CL; 3. Willingness to attend all visits (treatment (1, 2 and 3) and follow-up (1, 2 and 3) regarding the study; 4. Patient can be contacted by phone, either directly or through family living (in the vicinity of Paramaribo.
Exclusion criteria
Exclusion criteria: 1. Patients with CL treated in the past 6 months; 2. Pregnancy or lactation; 3. Potential loss to follow up (unable to attend one of the study visits, either treatment or follow-up visits; 4. Patients with a history of liver disease and/or elevated transaminasen levels of more than 2 times the normal value (normal values = 40% the upper limit of the normal range (normal values = 70-110 umol/l) at the time of enrollment; 6. Patients with a history of pancreas disease and/or elevated amylase levels of more than 3 times the normal value (normal value = 32 U/l) at the time of enrollment; 7. Patients with anemia (hemoglobin level < 7.5 mmol/l), leucocytopenia (leucocytes < 4x109/l) and thrombopenia (thrombocytes < 150x109/l) at the time of enrollment; 8. Patients with a history of heart disease; 9. Patients with diabetes; 10. Patients with a known allergy for Pentamidine Isethionate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish if a short course pentamidine isethionate 7 mg/kg body weight given intramuscular at days 1 and 3 (short course) is equally effective as the standard course pentamidine isethionate 4mg/kg intramuscular at days 1, 4 and 7 (standard course) in patients with CL. CL is diagnosed by the detection of leishmaniasis organisms (in a skin smear or a biopsy by light microscope or by the detection of leishmaniasis nucleic acid sequences through NAAT) in a clinically suspected lesion. 1. A clinical relapse is defined as persistence of one or more leishmaniasis lesions at 6 or 12 weeks after completion of treatment documented by one dermatologist with at least 4 years diagnostic experience in leishmaniasis. All lesions will be photographed (both healed and persisting lesions) and evaluated per visit by a second dermatologist with at least 4 years diagnostic experience in leishmaniasis, who is blinded from the results of the first evaluator. In case of discrepancy between the 2 dermatologist observers, the discrepancy will be solved by a third dermatologist with at least 4 years diagnostic experience in leishmaniasis on the basis of the photographs of the discrepant lesions. The expected success of the standard treatment group is approximately 90%10. To determine whether the treatment success of the short course is equal to that of the standard course, no less than an expected 70% treatment success is considered effective. 2. To establish if the short course is equally effective as the standard course as far as parasitological cure rate 6 and 12 weeks after completion of the treatment. A parasitological cure is defined as elimination of leishmania RNA 6 and 12 weeks after completion of the treatment course, in one designated proven leishmania RNA positive lesion before treatment. The short course is considered to have an equal parasitological cure rate, if in the short course arm the rate does not exceed the cure rate in the standard course arm by more than 20% (c | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To establish if the short course has an equal rate of patient reported side effects and clinically determined drug related toxicity events as the standard course. Side effects (recorded at the last treatment visit) are: a. nausea (as indicated by the patient); b. erythema exsudativum multiforme (occurrence of blisters in skin and/or mucosal tissue); c. unknown/other side effects. Drug related toxicity events (recorded 1 week after treatment and compared to the screenings visit) are: d. hypotension (10mm Hg drop in diastolic blood pressure compared to: the pressure before the injection, measured halfway the injection and 10 minutes after the injection); e. hemolysis (>1mmol drop in hemoglobin count); f. leucopenia (drop in leukocytes count 2 fold rise in serum transaminases, normal values = 10umol/l, normal values = 70-110 umol/l)); k. pancreas toxicity (3 fold rise in amylase, normal value = 32 U/l)). The short course is considered to have an equal rate of side effects or drug related drug toxicity events if in the short course arm the rate does not exceed the rate in the standard course arm by more 20%. 2. To establish if the short course is equal to the standard course as far as health related quality of life measured by validated self-report questionnaires. Generic QoL measured by the EQ-5D and EQ-VAS questionnaires and disease-specific QoL measured by the SKINDEX questionnaire. The short course is considered to affect the quality of life equally as the standard course if the quality of life outcome in the short course arm is no lower than the quality of life outcomes in the standard course group by more than 20%. 3. To establish if the short course is equal to the standard course as far as the cost-effectiveness based on a cost survey questionnaire. The appropriate type of economic evaluation is conditional on the results of the primary objective (relapse rate) and health related quality-of-life (HR-QoL). In the case of one clearly superior s | — |
Contacts
Public ContactRicardo Hu
Outcome results
None listed