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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04268524
Recruitment Status : Not yet recruiting
First Posted : February 13, 2020
Last Update Posted : June 18, 2020
Information provided by (Responsible Party):
Medecins Sans Frontieres, Netherlands

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Old World Cutaneous Leishmaniasis Combination Product: drug: miltefosine with thermotherapy Phase 3

Detailed Description:

Until now, there is no well-established evidence based option to treat CL caused by the Leishmania tropica, besides antimonial injections. Alternative treatment options are not available in Pakistan, or there is limited evidence of the effectivity.

Effectiveness of thermotherapy in L. tropica is studied in only three studies in OWCL with a variable cure rate (54.1% - 98%). But it could be an attractive option, because only one treatment session is required and studies report less scarring tissue. Another promising treatment option is oral miltefosine. There is considerable evidence in the literature of the efficacy of miltefosine in treatment of CL caused by L. major, however no studies have been conducted to evaluate the efficacy in CL caused by L. tropica species. This oral treatment could have major benefits for CL patients as it can be provided in peripheral health facilities and to patients who have contraindications to antimony treatment (elderly, and patients with cardiac or renal disease, or diabetes). A combination of thermotherapy and miltefosine, the advantages offered by this combination are that a) the use of a topical plus a systemic treatment would hypothetically have an additive effect of two treatments with different modes of action. For the reason that systemic treatment could eliminate those circulating or remaining parasites located in the periphery of the lesion that topical treatment fails to remove, which might be the cause of a relapse, b) it may reduce the necessary length of treatment with miltefosine. For these above reasons, in a prospective trial we aim to evaluate the effectiveness and safety of thermotherapy, miltefosine and the combination of thermotherapy and miltefosine in CL caused by L. tropica, with the objective to find a treatment with an efficacy which is non-inferior to the standard of care with antimony injections.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 832 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomised control trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomised, Open Label, Multicentre, Non-inferiority Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan
Estimated Study Start Date : February 1, 2021
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leishmaniasis
Drug Information available for: Miltefosine

Arm Intervention/treatment
Experimental: monotherapy miltefosine
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
see previous
Other Name: device ThermoMed 1.8

Experimental: Thermotherapy
Thermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session
Combination Product: drug: miltefosine with thermotherapy
see previous
Other Name: device ThermoMed 1.8

Experimental: Combination miltefosine and thermotherapy
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.
Combination Product: drug: miltefosine with thermotherapy
see previous
Other Name: device ThermoMed 1.8

Active Comparator: ° Meglumine antimoniate (Glucantime®) intralesional
Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly
Combination Product: drug: miltefosine with thermotherapy
see previous
Other Name: device ThermoMed 1.8

Primary Outcome Measures :
  1. The initial clinical cure rate in each study arm [ Time Frame: by Day 91. ]
    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.

  2. Adverse events [ Time Frame: by Day 91. ]
    Frequency, severity and seriousness of AEs by treatment group

Secondary Outcome Measures :
  1. initial cure and no relapse [ Time Frame: initial cure at D91 and have no relapse by D120. ]
    The proportion of patients in each study arm who have fulfilled the criteria of initial cure and have no relapse

  2. 100% re-epithelialized/ flattened [ Time Frame: at visit until D120 ]
    The number of patients with lesions 100% re-epithelialized/ flattened at each measurement time point.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Pregnant women and breast feeding women
  • Non-pregnant women in reproductive age refusing effective (injectable) contraception for a period of five months
  • Patients <10years 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 excipients
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04268524

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Contact: Suzette Kämink +31687680573
Contact: Koert Ritmeijer +31205208767

Sponsors and Collaborators
Medecins Sans Frontieres, Netherlands
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Study Director: Koert Ritmeijer Medecins Sans Frontieres, Netherlands
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Responsible Party: Medecins Sans Frontieres, Netherlands Identifier: NCT04268524    
Other Study ID Numbers: CL_RCT_MF_vs_TT_2020
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Plan need to be made what wilkl be shared with whom (such as study protocol, SAP, ICF etc)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Medecins Sans Frontieres, Netherlands:
Additional relevant MeSH terms:
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Leishmaniasis, Cutaneous
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Antifungal Agents
Anti-Infective Agents
Antineoplastic Agents
Antiprotozoal Agents
Antiparasitic Agents