Randomized Single-Blinded Non-inferiority Trial Of 7 mg/kg Pentamidine Isethionate Versus 4 mg/kg Pentamidine Isethionate for Cutaneous Leishmaniaisis in Suriname

Background: Standard treatment of cutaneous leishmaniasis (CL) in Suriname entails three injections of pentamidine isethionate (PI) 4 mg/kg per injection in 7 days (7 day regimen). Compliance to treatment is low and may contribute to increasing therapy failure. A 3 day regimen, including 2 injections of 7 mg/kg in 3 days may increase compliance. Methods: In a randomized, single-blinded non-inferiority trial conducted in Suriname, 84 CL patients received the 7 day regimen and 79 CL patients received the 3 day regimen. Primary objective was the proportion of patients clinically cured at 6 weeks follow-up. Secondary objectives were clinical cure at 12 weeks follow-up; parasitological cure at 6 and 12 weeks; adverse and drug related toxicity events recorded one week after the end of treatment and health related quality of life. The non-inferiority margin was set at 15%, 1 sided test, α = 0.1. Results: At 6 weeks follow-up 31 (39%) patients in the 3 day regimen and 41 (49%) patients in the 7 day regimen were clinically cured. Intention to treat (ITT) analyses showed that the difference in proportion clinically cured was -9.6% (90% Confidence Interval (CI): -22.3% to 3.2%). Per protocol (PP) analysis showed that the difference in proportion clinically cured was 0.2% (90% CI: -14.6% to 15.2%). ITT analysis showed that the difference in proportion parasitological cured at 6 weeks was -15.2% (90% CI:-28.0% to -2.5%). PP analyses showed similar results. Non-inferiority could not be concluded for all adverse and toxicological events. Conclusion: We cannot conclude that the 3 day regimen is non-inferior to the 7 day regimen regarding proportion clinically and parasitological cured. Therefore there is no evidence to change the current standard practice of the 7 day regimen for the treatment of CL in Suriname. Author Summary: Cutaneous Leishmaniasis (CL), caused by the single cellular protozoan parasite of the genus Leishmania, is treated in Suriname with pentamidine isethionate (PI). Standard treatment consists of 3 intramuscular injections of 4 mg per kg bodyweight given in 7 days. Compliance to treatment is low which may lead to treatment failure. A shorter treatment course of PI, 3 days, may aid in solving the compliance problem. In this study CL patients were included in two study arms, the control arm, PI 4 mg/kg/injection, three injections in 7 days (84 patients) and the intervention arm, PI 7 mg/kg/injection, two injections in 3 days (79 patients). Based on the study results it cannot be concluded that that the 3 day regimen is at least as good (non-inferior) to the 7 day regimen, as far as clinical and parasitological cure, toxic and adverse events. Based on these findings there is no evidence to change the standard treatment of 3 injections of 4 mg/kg PI in Suriname.