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

نویسندگان

  • Shyam Sundar
  • Prabhat Kumar Sinha
  • Madhukar Rai
  • Deepak Kumar Verma
  • Kumar Nawin
  • Shanawwaj Alam
  • Jaya Chakravarty
  • Michel Vaillant
  • Neena Verma
  • Krishna Pandey
  • Poonam Kumari
  • Chandra Shekhar Lal
  • Rakesh Arora
  • Bhawna Sharma
  • Sally Ellis
  • Nathalie Strub-Wourgaft
  • Manica Balasegaram
  • Piero Olliaro
  • Pradeep Das
  • Farrokh Modabber
چکیده

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. FUNDING Drugs for Neglected Diseases initiative and the Indian Council of Medical Research.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Treatment of Indian visceral leishmaniasis with single or daily infusions of low dose liposomal amphotericin B: randomised trial.

OBJECTIVE To test short course, low dose liposomal amphotericin B as single or daily infusion treatment in Indian visceral leishmaniasis (kala-azar). DESIGN Randomised, open label study. SETTING Inpatient unit for leishmaniasis in Bihar, India. PARTICIPANTS 91 adults and children with splenic aspirate positive for infection. INTERVENTIONS Total dose of 5 mg/kg of liposomal amphotericin ...

متن کامل

Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

BACKGROUND Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and m...

متن کامل

Development and evaluation of macrophage targeted multidrug therapy against visceral leishmaniasis

In this study, we fabricated PCL-nanoparticles by encapsulating dual drugs as amphotericin B and doxorubicin via double-emulsion solvent evaporation method also incorporated with ligand-lectin for targeting the infested macrophage cells and prove importance against VL. Different independent processing parameters were assessed systematically to enhance the incorporation of the dual agents with d...

متن کامل

Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial.

BACKGROUND Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication. METHODS We did a randomised, open-label, non-inferiority, phase 3 ...

متن کامل

A comparison between the efficacy of intralesional injection of 2% Zinc Sulfate solution with Glucantime in the treatment of acute old world cutaneous Leishmaniasis: A randomized, double-blind, controlled clinical trial

Background: Several treatment modalities have been used for cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of zinc sulfate (ZnSO4) on Leishmania parasites. Objective: To compare the efficacy of intralesional injections of 2% ZnSO4 solution with meglumine antimonate (Glucantime) in the treatment of acute Old World CL. Patients ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Lancet

دوره 377 9764  شماره 

صفحات  -

تاریخ انتشار 2011