Randomised Clinical Trial in Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan

NCT04268524 | Completed Phase 3 DMC

• 1 other identifier: CL_RCT_MF_vs_TT_2020
• Study Type: interventional
• Target: 645
• Locations: 1 country
• Sites: 3

Brief Summary

A four (4) -arm randomised control clinical trial to evaluate miltefosine, thermotherapy and the combination miltefosine-thermotherapy are effective, safe and tolerable alternative treatment options to treat cutaneous leishmaniasis caused by L. tropica, in Pakistan compared to the standard of care.

Conditions

Old World Cutaneous Leishmaniasis

Keywords

miltefosine; Thermotherapy; cutaneous leishmaniasis; Pakistan

Outcome Measures

Primary Outcomes (2)

• The initial clinical cure rate in each study arm

  Initial Cure: Ulcerated lesions: 100% re-epithelialization of the lesion(s) Non-Ulcerated lesions: flattening and/or no signs of induration of the lesion(s) by Day 91.

  by Day 91.

• Adverse events

  Frequency, severity and seriousness of AEs by treatment group

  by Day 91.

Secondary Outcomes (2)

• initial cure and no relapse

  initial cure at D91 and have no relapse by D120.

• 100% re-epithelialized/ flattened

  at visit until D120

Study Arms (4)

monotherapy miltefosine

EXPERIMENTAL

Miltefosine capsules (Impavido®) 2.5 mg/kg daily PO for 28 days \<30 kg BW allometric miltefosine dose based on fat-free mass. (approx. 2.5 mg/kg); \>30 - ≤44kg BW: 100 mg/day BID; ≥45kg BW 150mg TDS

Combination Product: drug: miltefosine with thermotherapy

Thermotherapy

OTHER

Thermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session: Discontinued Nov 2023

Combination Product: drug: miltefosine with thermotherapy

Combination miltefosine and thermotherapy

OTHER

Miltefosine capsules 2.5 mg/kg daily PO for 21days, and thermotherapy 50°C for 30 seconds, one session on day 1 of the miltefosine. Discontineud Dec.2024

Combination Product: drug: miltefosine with thermotherapy

° Meglumine antimoniate (Glucantime®) intralesional

ACTIVE COMPARATOR

Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly

Interventions

drug: miltefosine with thermotherapy COMBINATION_PRODUCT

see previous

Also known as: device ThermoMed 1.8

Combination miltefosine and thermotherapy; Thermotherapy; monotherapy miltefosine

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients with clinical and laboratory confirmed CL, and who can be treated with localised intralesional antimonial injections and/or thermotherapy:
• lesion size ≥0.5 cm and ≤4 cm
• not located on the ear, nose, near to the eye or mucosal membranes, on joints, or on a location that in the opinion of the principle investigator (PI) is difficult to apply thermotherapy (TT) or intralesional (IL) injections
• patient with ≤4 lesions
• duration of lesions less than five months by patient history
• Patients who have signed the informed consent form.
• After adaptation : (end Dec 2024) one eligible criteria changed :
• age from 10 to 6; all children from 6 years and older are eligible

You may not qualify if:

• Pregnant women and breast feeding women
• Non-pregnant women in reproductive age refusing effective (injectable) contraception for a period of five months
• Patients \<6years old
• Patients who cannot be treated with localised IL antimonial injections or TT (patients with more than 4 lesions, lesions \>4cm in diameter, or located on joints, lips, nose, ears or near eyes)
• History of clinically significant medical problems or treatment that might interact with the study treatment and interact with wound healing, such as diabetes, vascular diseases and any immunocompromising condition
• Within eight weeks of trial D1 received treatment for leishmaniasis with any medication
• History of known or suspected hypersensitivity of idiosyncratic reactions to trial medication or experiments
• Has laboratory values at screening: serum creatinine above normal level; ALT 3 times above normal range
• Patient who is not willing to attend the trial visits, or is not able to comply with follow-up visits up to three months.
• Known history of drug addiction and/or alcohol abuse
• age from 10 to 6 yrs, Children \< 6 years are excluded

Sponsors & Collaborators

• Medecins Sans Frontieres, Netherlands: lead

Study Sites (3)

Bolan Medical Complex Hospital

Quetta, Balochistan, Pakistan

Location

Kuchlak Primary Health Care Centre (MCH), Kuchlak, Pakistan

Quetta, Balochistan, Pakistan

Location

Shaheed Mohtarma Benazir Bhutto General Hospital

Quetta, Balochistan, Pakistan

Location

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Hyperthermia

Interventions

miltefosine; Hyperthermia, Induced

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Koert Ritmeijer

  Medecins Sans Frontieres, Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomised control trial

Study Record Dates

• First Submitted: February 11, 2020
• First Posted: February 13, 2020
• Study Start: October 7, 2022
• Primary Completion: June 19, 2026
• Study Completion: June 19, 2026
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF, CSR
• Time Frame: Early 2027

Locations

PA (3)