Comparison of short-course multidrug treatment with standard therapy for visceral leishmaniasis in India: an open-label, non-inferiority, randomised controlled trial

被引：241

作者：

Sundar, Shyam ^{[1
]}

Sinha, Prabhat Kumar ^{[2
]}

Rai, Madhukar ^{[1
]}

Verma, Deepak Kumar ^{[1
]}

Nawin, Kumar ^{[2
]}

Alam, Shanawwaj ^{[1
]}

Chakravarty, Jaya ^{[1
]}

Vaillant, Michel ^{[3
]}

Verma, Neena ^{[2
]}

Pandey, Krishna ^{[2
]}

Kumari, Poonam ^{[1
]}

Lal, Chandra Shekhar ^{[2
]}

Arora, Rakesh ^{[1
]}

Sharma, Bhawna ^{[4
]}

Ellis, Sally ^{[4
]}

Strub-Wourgaft, Nathalie ^{[4
]}

Balasegaram, Manica ^{[4
]}

Olliaro, Piero ^{[5
]}

Das, Pradeep ^{[2
]}

Modabber, Farrokh ^{[4
]}

机构：

[1] Banaras Hindu Univ, Inst Med Sci, Dept Med, Kala Azar Med Res Ctr, Varanasi 221005, Uttar Pradesh, India

[2] Indian Council Med Res, Rajendra Mem Res Inst Med Sci, Patna, Bihar, India

[3] Ctr Etud Sante, Ctr Rech Publ Sante, Luxembourg, Luxembourg

[4] Drugs Neglected Dis Initiat, Geneva, Switzerland

[5] WHO, WHO Special Programme Res & Training Trop Dis, World Bank, United Nations Dev Programme,UNICEF, CH-1211 Geneva, Switzerland

来源：

LANCET | 2011年 / 377卷 / 9764期

关键词：

LIPOSOMAL AMPHOTERICIN-B; COMBINATION THERAPIES; ORAL MILTEFOSINE; DRUG-RESISTANCE; IN-VITRO; SINGLE; PAROMOMYCIN; DONOVANI;

D O I：

10.1016/S0140-6736(10)62050-8

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Improved treatment approaches are needed for visceral leishmaniasis. We assessed the efficacy and safety of three potential short-course combination treatments compared with the standard monotherapy in India. Methods Standard treatment (1 mg/kg amphotericin B infusion on alternate days for 30 days, total dose 15 mg/kg) was compared with three drug combinations (single injection of 5 mg/kg liposomal amphotericin B and 7-day 50 mg oral miltefosine or single 10-day 11 mg/kg intramuscular paromomycin; or 10 days each of miltefosine and paromomycin) in an open-label, parallel-group, non-inferiority, randomised controlled trial in two hospital sites in Bihar, India. Patients aged 5-60 years with parasitologically confirmed visceral leishmaniasis were randomly assigned one of the four treatments by the trial statistician by use of a computer-generated list. Clinical assessments were done at the end of treatment (15 days on combination treatment; 31 days for standard treatment) and after 45 days and 6 months. The primary endpoint was definitive cure (defined as no sign or symptom of visceral leishmaniasis and parasitologically cured to the last follow-up). Analyses were done both by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00696969. Findings Between June, 2008, and July, 2009, 634 patients were assigned amphotericin B (n=157), liposomal amphotericin B with miltefosine (n=160) or paromomycin (n=158), or miltefosine and paromomycin (n=159). 618 patients were in the per-protocol population. There were two relapses in each group. The numbers with definitive cure at 6 months for the intention-to-treat population were 146 (cure rate 93.0%; CI 87.5-96.3) for amphotericin B, 156 (97.5%; 93.3-99.2) for liposomal amphotericin B and miltefosine, 154 (97.5%; 93.24-99.2) for liposomal amphotericin B and paromomycin, and 157(98-7%; 95.1-99.8) for miltefosine and paromomycin. All combinations were non-inferior to the standard treatment, in both the intention-to-treat and per-protocol populations. Patients in the combination groups had fewer adverse events than did those assigned standard treatment. Interpretation Combination treatments for visceral leishmaniasis are efficacious and safe, and decrease the duration of therapy, thereby encouraging adherence and reducing emergence of drug-resistant parasites.

引用

页码：477 / 486

页数：10

共 24 条

[1]

[Anonymous], 2009, RES SUPP EL VISC LEI

[2] Of Cattle, Sand Flies and Men: A Systematic Review of Risk Factor Analyses for South Asian Visceral Leishmaniasis and Implications for Elimination [J].