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Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial.
Trials. 2011 Jun 30; 12:166.T

Abstract

BACKGROUND

Treatment options for visceral leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.

METHODS/DESIGN

A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure.

DISCUSSION

A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes.

TRIAL REGISTRATION

ClinicalTrials.gov: NCT01067443.

Authors+Show Affiliations

Drugs for Neglected Diseases initiative (DNDi) Africa, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21718522

Citation

Omollo, Raymond, et al. "Safety and Efficacy of Miltefosine Alone and in Combination With Sodium Stibogluconate and Liposomal Amphotericin B for the Treatment of Primary Visceral Leishmaniasis in East Africa: Study Protocol for a Randomized Controlled Trial." Trials, vol. 12, 2011, p. 166.
Omollo R, Alexander N, Edwards T, et al. Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials. 2011;12:166.
Omollo, R., Alexander, N., Edwards, T., Khalil, E. A., Younis, B. M., Abuzaid, A. A., Wasunna, M., Njoroge, N., Kinoti, D., Kirigi, G., Dorlo, T. P., Ellis, S., Balasegaram, M., & Musa, A. M. (2011). Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials, 12, 166. https://doi.org/10.1186/1745-6215-12-166
Omollo R, et al. Safety and Efficacy of Miltefosine Alone and in Combination With Sodium Stibogluconate and Liposomal Amphotericin B for the Treatment of Primary Visceral Leishmaniasis in East Africa: Study Protocol for a Randomized Controlled Trial. Trials. 2011 Jun 30;12:166. PubMed PMID: 21718522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. AU - Omollo,Raymond, AU - Alexander,Neal, AU - Edwards,Tansy, AU - Khalil,Eltahir A G, AU - Younis,Brima M, AU - Abuzaid,Abuzaid A, AU - Wasunna,Monique, AU - Njoroge,Njenga, AU - Kinoti,Dedan, AU - Kirigi,George, AU - Dorlo,Thomas P C, AU - Ellis,Sally, AU - Balasegaram,Manica, AU - Musa,Ahmed M, Y1 - 2011/06/30/ PY - 2011/03/21/received PY - 2011/06/30/accepted PY - 2011/7/2/entrez PY - 2011/7/2/pubmed PY - 2011/11/16/medline SP - 166 EP - 166 JF - Trials JO - Trials VL - 12 N2 - BACKGROUND: Treatment options for visceral leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa. METHODS/DESIGN: A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure. DISCUSSION: A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01067443. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/21718522/Safety_and_efficacy_of_miltefosine_alone_and_in_combination_with_sodium_stibogluconate_and_liposomal_amphotericin_B_for_the_treatment_of_primary_visceral_leishmaniasis_in_East_Africa:_study_protocol_for_a_randomized_controlled_trial_ L2 - https://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-12-166 DB - PRIME DP - Unbound Medicine ER -