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Trial of oral miltefosine for visceral leishmaniasis.
Lancet. 1998 Dec 05; 352(9143):1821-3.Lct

Abstract

BACKGROUND

There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar.

METHODS

Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse.

FINDINGS

21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed.

INTERPRETATION

Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.

Authors+Show Affiliations

Kala-Azar Medical Research Center, Banaras Hindu University Institute of Medical Sciences, Varanasi, India.No 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
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9851383

Citation

Sundar, S, et al. "Trial of Oral Miltefosine for Visceral Leishmaniasis." Lancet (London, England), vol. 352, no. 9143, 1998, pp. 1821-3.
Sundar S, Rosenkaimer F, Makharia MK, et al. Trial of oral miltefosine for visceral leishmaniasis. Lancet. 1998;352(9143):1821-3.
Sundar, S., Rosenkaimer, F., Makharia, M. K., Goyal, A. K., Mandal, A. K., Voss, A., Hilgard, P., & Murray, H. W. (1998). Trial of oral miltefosine for visceral leishmaniasis. Lancet (London, England), 352(9143), 1821-3.
Sundar S, et al. Trial of Oral Miltefosine for Visceral Leishmaniasis. Lancet. 1998 Dec 5;352(9143):1821-3. PubMed PMID: 9851383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trial of oral miltefosine for visceral leishmaniasis. AU - Sundar,S, AU - Rosenkaimer,F, AU - Makharia,M K, AU - Goyal,A K, AU - Mandal,A K, AU - Voss,A, AU - Hilgard,P, AU - Murray,H W, PY - 1998/12/16/pubmed PY - 1998/12/16/medline PY - 1998/12/16/entrez SP - 1821 EP - 3 JF - Lancet (London, England) JO - Lancet VL - 352 IS - 9143 N2 - BACKGROUND: There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar. METHODS: Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. FINDINGS: 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. INTERPRETATION: Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection. SN - 0140-6736 UR - https://www.unboundmedicine.com/medline/citation/9851383/Trial_of_oral_miltefosine_for_visceral_leishmaniasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(98)04367-0 DB - PRIME DP - Unbound Medicine ER -