Old World Cutaneous LeishmaniasisPhase 3NCT04268524
Randomised Clinical Trial in Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan
A Phase 3 study testing drug: miltefosine with thermotherapy in people with Old World Cutaneous Leishmaniasis, run by Medecins Sans Frontieres, Netherlands at 3 sites in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Old World Cutaneous Leishmaniasis
- What is being tested?
- drug: miltefosine with thermotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 645 participants
- Where
- 3 sitesPakistan
- Study dates
- 7 Oct 2022to 19 Jun 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
- After adaption (end Dec 2024) one exclusion criteria changed:
- age from 10 to 6 yrs, Children < 6 years are excluded
- -
Trial locations and contacts
3 sites in 1 country.
Pakistan3 sites
Bolan Medical Complex Hospital
Quetta, Balochistan
Kuchlak Primary Health Care Centre (MCH), Kuchlak, Pakistan
Quetta, Balochistan
Shaheed Mohtarma Benazir Bhutto General Hospital
Quetta, Balochistan
About this study
Official title: Randomised, Open Label, Multicentre, Non-inferiority Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan
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.
Read the 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.
Update on trial adaptations:
As pre-specified in the trial design, a futility analysis was planned after recruitment of approximately 30% of participants. Following this analysis, the thermotherapy arm was discontinued due to futility as per November 2023 At a subsequent interim analysis, the Data and Safety Monitoring Board (DSMB) recommended also to discontinue the combination arm (thermotherapy plus miltefosine), as no added value of thermotherapy could be demonstrated (as per January 2025)
The trial continues with the only two (2) arms: oral miltefosine and the standard of care with antimonial injections.
- Conditions
- Old World Cutaneous Leishmaniasis
- Being tested
- drug: miltefosine with thermotherapy
- Keywords
- miltefosine, Thermotherapy, cutaneous leishmaniasis, Pakistan
- Medical subject headings
- Leishmaniasis, Cutaneous, Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
drug: miltefosine with thermotherapyCombination product
Also called device ThermoMed 1.8
see previous
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Combination Product: drug: miltefosine with thermotherapy |
| Thermotherapy | Other | Thermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session: Discontinued Nov 2023 Receives: 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 Receives: Combination Product: drug: miltefosine with thermotherapy |
| ° Meglumine antimoniate (Glucantime®) intralesional | Active comparator | Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: by Day 91.
Adverse events
Frequency, severity and seriousness of AEs by treatment group
Measured: by Day 91.
Secondary outcomes (2)
initial cure and no relapse
The proportion of patients in each study arm who have fulfilled the criteria of initial cure and have no relapse
Measured: initial cure at D91 and have no relapse by D120.
100% re-epithelialized/ flattened
The number of patients with lesions 100% re-epithelialized/ flattened at each measurement time point.
Measured: at visit until D120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start7 Oct 2022
- Primary completion19 Jun 2026
- Study completion19 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Old World Cutaneous LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomised control trial
- Masking
- None (open label)
- Enrolment
- 645 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medecins Sans Frontieres, Netherlands
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Koert Ritmeijer, Study director, Medecins Sans Frontieres, Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04268524
- Sponsor's protocol ID
- CL_RCT_MF_vs_TT_2020
- Status last verified
- Jul 2026
- First submitted
- 11 Feb 2020
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Plan need to be made what will be shared with whom (such as study protocol, SAP, ICF etc)
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised, Open Label, Multicentre, Non-inferiority Clinical Trial for New Treatment Modalities for Cutaneous Leishmaniasis Caused by Leishmania Tropica, in Pakistan
- ClinicalTrials.gov ID
- NCT04268524
- Acronym / sponsor ID
- CL_RCT_MF_vs_TT_2020
- Conditions
- Old World Cutaneous Leishmaniasis
- Keywords
- miltefosine, Thermotherapy, cutaneous leishmaniasis, Pakistan
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 645 participants (actual)
- Lead sponsor
- Medecins Sans Frontieres, NetherlandsUniversity, hospital or other
- Study start
- 7 Oct 2022 (actual)
- Primary completion
- 19 Jun 2026 (actual)
- Study completion
- 19 Jun 2026 (actual)
- First posted
- 13 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Update on trial adaptations:
As pre-specified in the trial design, a futility analysis was planned after recruitment of approximately 30% of participants. Following this analysis, the thermotherapy arm was discontinued due to futility as per November 2023 At a subsequent interim analysis, the Data and Safety Monitoring Board (DSMB) recommended also to discontinue the combination arm (thermotherapy plus miltefosine), as no added value of thermotherapy could be demonstrated (as per January 2025)
The trial continues with the only two (2) arms: oral miltefosine and the standard of care with antimonial injections.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- randomised control trial
| Arm | Type | Receives |
|---|---|---|
| monotherapy miltefosine | Experimental | Combination Product: drug: miltefosine with thermotherapyMiltefosine 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 |
| Thermotherapy | Other | Combination Product: drug: miltefosine with thermotherapyThermotherapy (ThermoMed 1.8 ®) 50°C for 30 seconds, 1 session: Discontinued Nov 2023 |
| Combination miltefosine and thermotherapy | Other | Combination Product: drug: miltefosine with thermotherapyMiltefosine 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 |
| ° Meglumine antimoniate (Glucantime®) intralesional | Active comparator | –Meglumine antimoniate (Glucantime®) intralesional injections 0.5-3ml, 8 sessions, bi-weekly |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| drug: miltefosine with thermotherapyAlso: device ThermoMed 1.8see previous | Combination product | Combination miltefosine and thermotherapy, Thermotherapy, monotherapy miltefosine |
Primary outcome
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.
Adverse events
Time frame: by Day 91.
Frequency, severity and seriousness of AEs by treatment group
2 secondary outcomes
initial cure and no relapse
Time frame: initial cure at D91 and have no relapse by D120.
100% re-epithelialized/ flattened
Time frame: at visit until D120
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- Individual participant dataSharing planned: Yes. Plan need to be made what will be shared with whom (such as study protocol, SAP, ICF etc)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koert Ritmeijer study director
Medecins Sans Frontieres, Netherlands
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing drug: miltefosine with thermotherapy in people with Old World Cutaneous Leishmaniasis, run by Medecins Sans Frontieres, Netherlands at 3 sites in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The initial clinical cure rate in each study arm (time frame: by Day 91.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2026.