Cutaneous LeishmaniasisPhase 2NCT02687971
Thermotherapy + a Short Course of Miltefosine for the Treatment of Uncomplicated Cutaneous Leishmaniasis in the New World¨
A Phase 2 study testing Miltefosine in people with Cutaneous Leishmaniasis, run by Drugs for Neglected Diseases at 2 sites in 2 countries.
Trial summary
The purpose of this trial is to determine the efficacy and safety of a combined therapy using thermotherapy (TT) (one session, 50 degrees Celsius for 30") + miltefosine at a standard dose of 2.5 mg/kg/day for 21 days for the treatment of uncomplicated CL in Peru and Colombia Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- Miltefosine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2016to 10 Sep 2019
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient with a confirmed diagnosis of CL in at least one lesion by at least one of the following methods: 1) microscopic identification of amastigotes in stained lesion tissue, or 2) demonstration of Leishmania by PCR, or 3) positive culture for promastigotes,
- Patient has a lesion that satisfies the following criteria:
- Lesion size ≥ 0.5 cm and </= 4 cm (Longest diameter),
- Not located on the ear, face, close to mucosal membranes, joints or on a location that in the opinion of the PI is difficult to apply TT,
- Patient with </= 4 CL lesions,
- Duration of lesion less than 4 months by patient history, Patient able to give written informed consent, In the opinion of the investigator, the patient is capable of understanding and complying with the protocol
Who cannot join
- Female with a positive urine pregnancy test at screening or who is breast feeding, lactating or female at fertile age who does not agree to take appropriate contraception during treatment period and up to D90,
- History of clinically significant medical problems / treatment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition,
- Within 8 weeks (56 days) of trial Day 1, received treatment for leishmaniasis with any medication including antimonials likely, in the opinion of the PI, to modify the course of the Leishmania infection,
- Has diagnosis or suspected diagnosis of mucocutaneous leishmaniasis based on physical exam,
- History of known or suspected hypersensitivity or idiosyncratic reactions to trial medication or exipients,
- Patient who is not willing to attend the trial visits, or is not able to comply with follow-up visits up to 6 months,
- Known history of drug addiction and/or alcohol abuse
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Colombia1 site
Programa de Estudios y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia
Medellín
About this study
Official title: A Randomized, Open Label, Multicenter Study to Determine the Efficacy and Safety of Combining Thermotherapy and a Short Course of Miltefosine for the Treatment of Uncomplicated Cutaneous Leishmaniasis in the New World¨
The purpose of this trial is to determine the efficacy and safety of a combined therapy using thermotherapy (TT) (one session, 50 degrees Celsius for 30") + miltefosine at a standard dose of 2.5 mg/kg/day for 21 days for the treatment of uncomplicated CL in Peru and Colombia
Read the detailed description
The use of topical treatments for Cutaneous leishmaniasis (CL) is an option that has been widely explored and it is currently listed as an options by WHO in those situations where the patient has few lesions (≤ 4) of less than ≤ 4 cm in diameter and located in areas of the body which may be treated topically.
Local heat, especially the one produced by radio frequency waves (Themo-Med®) has been widely tested for CL in both Old and New World. The advantages of using thermotherapy include: 1) high security profile; 2) only one session is required which ensures compliance with treatment; 3) easy to use in the field since the machine operates with batteries; 4) its effectiveness does not depend on the species of Leishmania causing the lesion as it is a physical measure; and 5) it can be used in patients in whom systemic treatment with antimonials are contraindicated, including women who are pregnant or breastfeeding. In the New World, Thermo-Med® has been evaluated in Mexico, Guatemala, Colombia and Brazil (all but one were randomized clinical trials), reporting cure rates of 90%, 73%, 64% and 75% respectively
There are no clinical trials evaluating the efficacy of miltefosine for CL when given for less than 20 days. The 21-day course was chosen to give the best chances to the combination approach and based on a) the results of a Phase II trial conducted in Colombia showing that a mean dose of miltefosine of 133 mg/day/20 days resulted in a cure rate of 82%20 and; b) a report showing that the a daily administration of 100 mg/day (2.5 mg/kg of body weight/day for 28 days) resulted in a mean maximum concentration of drug in serum at day 23 of treatment of 70,000 ng/ml21.
The theoretical advantages offered by this combination are that a) we are using two approaches that are currently recommended for use individually and for which there is good information regarding their efficacy and safety when used alone; b) the use of a topical plus a systemic treatment would hypothetically have an additive effect, since systemic treatment would eliminate those circulating or remaining parasites located in the periphery of the lesion that topical treatment fails to remove and which might be the cause of relapses22,23; c) it offers the opportunity to increase the current cure rate reported with any other treatment approach available when used alone; d) it will reduce the length of treatment with miltefosine and hopefully the cost and rates of adverse events associated with 28 days of treatment with miltefosine.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- Miltefosine
- Medical subject headings
- Leishmaniasis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MiltefosineDrug
Also called Impavido
Miltefosine (hexadecylphosphocholine) is an oral drug which has proven to be effective for the treatment of Visceral leishmaniasis (VL) in the Indian sub-continent. It has also been tested for CL, yielding varying results. Miltefosine was approved by FDA in 2014 for the treatment of CL in the New World for lesions due to L. braziliensis, L. panamensis and L. guyanensis only.
| Study group | Role | What they receive |
|---|---|---|
| Thermotherapy alone | Active comparator | Local heat will be applied using a Localized Current Field radio-frequency generating device manufactured by Thermo-Med Technologies, Inc. A wand with 2 electrodes is connected to the main housing by a thin wire. The electrodes are applied to the skin. We will use electrodes 6 mm long, separated by 4 mm. One single session at the site of the lesion(s) at 50°C for 30" applications will be used. Depending on the size of the lesion, more than one application may be administered. Receives: Drug: Miltefosine |
| Thermotherapy plus Miltefosine | Experimental | In addition to receiving one single session of thermotherapy as described above, subjects will receive oral miltefosine two or three capsules a day, which is the equivalent of 100 to 150mg respectively for 21 days. Miltefosine capsules will be taken after breakfast, lunch and dinner, in other words, after food.
The daily dose of miltefosine will depend on the weight of each patient. According to dosage instructions if the patient is taking the miltefosine twice a day, it must be taken in the morning and night (dose of 100mg/Kg/day). Whereas if the patient is taking miltefosine three times a day, it must be taken in the morning, noon and night (dose of 150mg/Kg/day). Receives: Drug: Miltefosine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Initial cure rate
Initial Cure: Ulcerated lesions: 100% re-epithelialization of the lesion(s) by Day 90.
Non-Ulcerated lesions: flattening and/or no signs of induration of the lesion(s) by Day 90.
The percentage of re-epithelialization of the lesion(s) is calculated by comparing the size of the ulcer at Day 7 against the size at the follow up visit
Measured: Day 90, after start of treatment
Secondary outcomes (2)
Final cure rate
The number of patients who fulfill the criteria of initial cure and have no relapse by Day 180
Measured: Day 180, after star of treatment
Frequency and severity of AEs
Frequency and severity of AEs by treatment group
Measured: Day 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study startDec 2016
- Primary completion10 Aug 2019
- Study completion10 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ivan Dario Velez, Prof, Principal investigator, PECET, Universidad de Antioquia, Medellin, ColombiaAlejandro Llanos-Cuentas, MD, PhD, Principal investigator, Universidad Peruana Cayetano Heredia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02687971
- Sponsor's protocol ID
- DNDi-MILT-07-CL
- Status last verified
- Sep 2019
- First submitted
- 17 Feb 2016
- Last updated
- 12 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lopez L, Valencia B, Alvarez F, Ramos AP, Llanos-Cuentas A, Echevarria J, Velez I, Boni M, Rode J, Quintero J, Jimenez A, Tabares Y, Mendez C, Arana B. A phase II multicenter randomized study to evaluate the safety and efficacy of combining thermotherapy and a short course of miltefosine for the treatment of uncomplicated cutaneous leishmaniasis in the New World. PLoS Negl Trop Dis. 2022 Mar 7;16(3):e0010238. doi: 10.1371/journal.pntd.0010238. eCollection 2022 Mar.
PubMed 35255096
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label, Multicenter Study to Determine the Efficacy and Safety of Combining Thermotherapy and a Short Course of Miltefosine for the Treatment of Uncomplicated Cutaneous Leishmaniasis in the New World¨
- ClinicalTrials.gov ID
- NCT02687971
- Acronym / sponsor ID
- DNDi-MILT-07-CL
- Conditions
- Cutaneous Leishmaniasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- 10 Aug 2019 (actual)
- Study completion
- 10 Sep 2019 (actual)
- First posted
- 23 Feb 2016 (estimated)
- 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.
The purpose of this trial is to determine the efficacy and safety of a combined therapy using thermotherapy (TT) (one session, 50 degrees Celsius for 30") + miltefosine at a standard dose of 2.5 mg/kg/day for 21 days for the treatment of uncomplicated CL in Peru and Colombia
Detailed description
The use of topical treatments for Cutaneous leishmaniasis (CL) is an option that has been widely explored and it is currently listed as an options by WHO in those situations where the patient has few lesions (≤ 4) of less than ≤ 4 cm in diameter and located in areas of the body which may be treated topically.
Local heat, especially the one produced by radio frequency waves (Themo-Med®) has been widely tested for CL in both Old and New World. The advantages of using thermotherapy include: 1) high security profile; 2) only one session is required which ensures compliance with treatment; 3) easy to use in the field since the machine operates with batteries; 4) its effectiveness does not depend on the species of Leishmania causing the lesion as it is a physical measure; and 5) it can be used in patients in whom systemic treatment with antimonials are contraindicated, including women who are pregnant or breastfeeding. In the New World, Thermo-Med® has been evaluated in Mexico, Guatemala, Colombia and Brazil (all but one were randomized clinical trials), reporting cure rates of 90%, 73%, 64% and 75% respectively
There are no clinical trials evaluating the efficacy of miltefosine for CL when given for less than 20 days. The 21-day course was chosen to give the best chances to the combination approach and based on a) the results of a Phase II trial conducted in Colombia showing that a mean dose of miltefosine of 133 mg/day/20 days resulted in a cure rate of 82%20 and; b) a report showing that the a daily administration of 100 mg/day (2.5 mg/kg of body weight/day for 28 days) resulted in a mean maximum concentration of drug in serum at day 23 of treatment of 70,000 ng/ml21.
The theoretical advantages offered by this combination are that a) we are using two approaches that are currently recommended for use individually and for which there is good information regarding their efficacy and safety when used alone; b) the use of a topical plus a systemic treatment would hypothetically have an additive effect, since systemic treatment would eliminate those circulating or remaining parasites located in the periphery of the lesion that topical treatment fails to remove and which might be the cause of relapses22,23; c) it offers the opportunity to increase the current cure rate reported with any other treatment approach available when used alone; d) it will reduce the length of treatment with miltefosine and hopefully the cost and rates of adverse events associated with 28 days of treatment with miltefosine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thermotherapy alone | Active comparator | Drug: MiltefosineLocal heat will be applied using a Localized Current Field radio-frequency generating device manufactured by Thermo-Med Technologies, Inc. A wand with 2 electrodes is connected to the main housing by a thin wire. The electrodes are applied to the skin. We will use electrodes 6 mm long, separated by 4 mm. One single session at the site of the lesion(s) at 50°C for 30" applications will be used. Depending on the size of the lesion, more than one application may be administered. |
| Thermotherapy plus Miltefosine | Experimental | Drug: MiltefosineIn addition to receiving one single session of thermotherapy as described above, subjects will receive oral miltefosine two or three capsules a day, which is the equivalent of 100 to 150mg respectively for 21 days. Miltefosine capsules will be taken after breakfast, lunch and dinner, in other words, after food. The daily dose of miltefosine will depend on the weight of each patient. According to dosage instructions if the patient is taking the miltefosine twice a day, it must be taken in the morning and night (dose of 100mg/Kg/day). Whereas if the patient is taking miltefosine three times a day, it must be taken in the morning, noon and night (dose of 150mg/Kg/day). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Patient with a confirmed diagnosis of CL in at least one lesion by at least one of the following methods: 1) microscopic identification of amastigotes in stained lesion tissue, or 2) demonstration of Leishmania by PCR, or 3) positive culture for promastigotes,
- Lesion size ≥ 0.5 cm and </= 4 cm (Longest diameter),
- Not located on the ear, face, close to mucosal membranes, joints or on a location that in the opinion of the PI is difficult to apply TT,
- Patient with </= 4 CL lesions,
- Duration of lesion less than 4 months by patient history, Patient able to give written informed consent, In the opinion of the investigator, the patient is capable of understanding and complying with the protocol
Key exclusion criteria (7 listed)
- Female with a positive urine pregnancy test at screening or who is breast feeding, lactating or female at fertile age who does not agree to take appropriate contraception during treatment period and up to D90,
- History of clinically significant medical problems / treatment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition,
- Within 8 weeks (56 days) of trial Day 1, received treatment for leishmaniasis with any medication including antimonials likely, in the opinion of the PI, to modify the course of the Leishmania infection,
- Has diagnosis or suspected diagnosis of mucocutaneous leishmaniasis based on physical exam,
- History of known or suspected hypersensitivity or idiosyncratic reactions to trial medication or exipients,
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 |
|---|---|---|
| MiltefosineAlso: ImpavidoMiltefosine (hexadecylphosphocholine) is an oral drug which has proven to be effective for the treatment of Visceral leishmaniasis (VL) in the Indian sub-continent. It has also been tested for CL, yielding varying results. Miltefosine was approved by FDA in 2014 for the treatment of CL in the New World for lesions due to L. braziliensis, L. panamensis and L. guyanensis only. | Drug | Thermotherapy alone, Thermotherapy plus Miltefosine |
Primary outcome
Initial cure rate
Time frame: Day 90, after start of treatment
Initial Cure: Ulcerated lesions: 100% re-epithelialization of the lesion(s) by Day 90. Non-Ulcerated lesions: flattening and/or no signs of induration of the lesion(s) by Day 90. The percentage of re-epithelialization of the lesion(s) is calculated by comparing the size of the ulcer at Day 7 against the size at the follow up visit
2 secondary outcomes
Final cure rate
Time frame: Day 180, after star of treatment
Frequency and severity of AEs
Time frame: Day 45
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 12 Sep 2019.
- Derived from this study: PubMed 35255096Lopez L, Valencia B, Alvarez F, Ramos AP, Llanos-Cuentas A, Echevarria J, Velez I, Boni M, Rode J, Quintero J, Jimenez A, Tabares Y, Mendez C, Arana B. A phase II multicenter randomized study to evaluate the safety and efficacy of combining thermotherapy and a short course of miltefosine for the treatment of uncomplicated cutaneous leishmaniasis in the New World. PLoS Negl Trop Dis. 2022 Mar 7;16(3):e0010238. doi: 10.1371/journal.pntd.0010238. eCollection 2022 Mar.
- Individual participant dataSharing planned: Undecided
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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.
Ivan Dario Velez, Prof principal investigator
PECET, Universidad de Antioquia, Medellin, Colombia
Alejandro Llanos-Cuentas, MD, PhD principal investigator
Universidad Peruana Cayetano Heredia
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Miltefosine in people with Cutaneous Leishmaniasis, run by Drugs for Neglected Diseases at 2 sites in 2 countries.
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 6 inclusion and 7 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 12 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Colombia, Peru. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Initial cure rate (time frame: Day 90, after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02687971, which also lists 1 linked publication.
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 12 Sep 2019.