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.

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 combination...

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Publicado en:Trials Vol. 12; no. 1; pp. 166 - 176
Autores principales: Omollo, Raymond, Alexander, Neal, Edwards, Tansy, Khalil, Eltahir A G, Younis, Brima M, Abuzaid, Abuzaid A, Wasunna, Monique, Njoroge, Njenga, Kinoti, Dedan, Kirigi, George, Dorlo, Thomas P C, Ellis, Sally, Balasegaram, Manica, Musa, Ahmed M
Formato: clinical trial research randomized controlled trial Journal Article
Publicado: BioMed Central 2011
Acceso en línea:Ver este registro en EBSCOhost
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      pub: BioMed Central
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        10.1186/1745-6215-12-166
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        atl: 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.
      aug:
        au:
          Omollo, Raymond
          Alexander, Neal
          Edwards, Tansy
          Khalil, Eltahir A G
          Younis, Brima M
          Abuzaid, Abuzaid A
          Wasunna, Monique
          Njoroge, Njenga
          Kinoti, Dedan
          Kirigi, George
          Dorlo, Thomas P C
          Ellis, Sally
          Balasegaram, Manica
          Musa, Ahmed M
        affil: Drugs for Neglected Diseases initiative (DNDi) Africa, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya
      sug:
        subj:
          Amphotericin B Therapeutic Use
          Study Design
          Leishmaniasis Drug Therapy
          Choline
          Antiprotozoal Agents Therapeutic Use
          Middle Age
          Leishmaniasis Diagnosis
          Antiprotozoal Agents Pharmacokinetics
          Antiprotozoal Agents Adverse Effects
          Time Factors
          Choline Pharmacokinetics
          Amphotericin B Adverse Effects
          Sudan
          Choline Therapeutic Use
          Treatment Outcomes
          Child
          Human
          Young Adult
          Kenya
          Adolescence
          Drug Therapy, Combination
          Adult
          Choline Adverse Effects
          Clinical Trials
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Randomized Controlled Trials
          Scales
          Middle Aged: 45-64 years
          Child: 6-12 years
          Adolescent: 13-18 years
          Adult: 19-44 years
      ab: 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.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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