Ignite Creation Date:
2025-12-24 @ 7:50 PM
Ignite Modification Date:
2025-12-25 @ 5:26 PM
Study NCT ID:
NCT07286604
Status:
COMPLETED
Last Update Posted:
2025-12-16
First Post:
2025-12-03
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Ivermectin Repurposed for the Treatment of PKDL
Sponsor:
International Centre for Diarrhoeal Disease Research, Bangladesh
Organization:
Study Overview
Official Title:
Repurposing Ivermectin (IVM) for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL): Safety and Response to Multiple Doses of Ivermectin
Status:
COMPLETED
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background (brief):
1. Burden: Post-Kala-Azar Dermal Leishmaniasis (PKDL) commonly follows visceral leishmaniasis (VL) caused by Leishmania donovani. It is characterized by skin lesions in which parasites can be identified, in a patient who is otherwise fully recovered from VL or exposed to L. donovani (LD) infection. It occurs in the Indian subcontinent (mainly India and Bangladesh) as well as in Africa (mainly Sudan). It is now established that PKDL patients play an important role in transmission of LD parasite where chronic PKDL patients have been implicated in major VL outbreaks in the past. In a series of cross-sectional surveys between 2002-2010, the cumulative incidence of PKDL was estimated at 17% by 5 years in Bangladesh. Most patients had been treated with SSG (95%); the mean interval between VL and PKDL was 19 months. A recent longitudinal study in Fulbaria (2015) of 1918 VL patients with active follow-up showed PKDL rates of 10.2% at 36 months (mean 17.6 months; range 4-43 months) after VL treated with 6 x 5 mg/kg Ambisome® (Koert Ritmeijer, MSF, personal communication). Though VL cases are in decline due to extensive programmes conducted by NKEP, PKDL cases are in the rise and VL:PKDL ratio has risen from 1:0.47 to 1:1.21 from 2016 to 2020. In this current situation, elimination of PKDL cases is of crucial importance in the current VL elimination efforts in Bangladesh as well as in the Indian subcontinent.
2. Knowledge gap: Currently there are no satisfactory treatments for any forms of PKDL. Available treatments include pentavalent antimonial sodium stibogluconate (Pentostam, Stibonate) which have been used since the 1940s. Conventional amphotericin B has been used in India for prolonged periods (60 infusions) but this is impractical and requires careful clinical and biochemical monitoring. Both miltefosine and Ambisome® as monotherapy have shown to be effective. However, with the current recommended scheme there are some drawbacks such as the length of the treatment with miltefosine alone (8-12 weeks), toxicity related to it; a high dose Ambisome® (total dose of 20 mg/kg) given frequently in 4 divided dosage often causes adverse events (e.g. pancytopania, hypokalemia, increased creatinine level etc.). There is also the potential risk for development of resistance with miltefosine as monotherapy. Ivermectin has been proven to have a significant leishmanicidal effect by several experimental studies at higher doses without significant toxicity and may offer shorter duration of treatment thus preventing prolonged hospitalization.
Another possible advantage is reduction of cost. These principles can be applied to PKDL, where the need for an ambulatory treatment with a highly safe, efficacious and user friendly regimen is even more pressing as the patients feel otherwise healthy, except for the rashes.
3. Relevance: This study aims primarily to improve current treatment options. In addition, this will be the first human study ever in PKDL in relation to Ivermectin, in which outcome will be described in clinical, parasitological and immunological terms. Ultimately this study findings will help National Kala-Azar Elimination Program (NKAEP) to adopt specific strategies for elimination of PKDL cases.
Hypothesis (if any): Oral ivermectin in multiple doses is safe and effective for the treatment of PKDL cases.
Objectives: To measure the safety and efficacy of Ivermectin monotherapy regimen (60 mg oral on five consecutive days, for three consecutive months) in treating PKDL patients in Bangladesh.
Methods: This will be a non-control, quasi-experimental, single group, proof of concept, intervention study to assess the safety and efficacy of oral Ivermectin monotherapy (5 x 12 mg daily at a total dose of 60 mg per month for three consecutive months, 180 mg in total) in treating PKDL patients in Bangladesh. In this study we are going to assess whether oral ivermectin in mentioned doses is effective for PKDL treatment or not. All participants will be recruited at SKKRC, Mymensingh with due consent. All patients will be followed up for 6 months since treatment. Cure assessment will be performed. Outcome measures/variables: Safety and efficacy of Ivermectin for PKDL treatment will be determined
1. Burden: Post-Kala-Azar Dermal Leishmaniasis (PKDL) commonly follows visceral leishmaniasis (VL) caused by Leishmania donovani. It is characterized by skin lesions in which parasites can be identified, in a patient who is otherwise fully recovered from VL or exposed to L. donovani (LD) infection. It occurs in the Indian subcontinent (mainly India and Bangladesh) as well as in Africa (mainly Sudan). It is now established that PKDL patients play an important role in transmission of LD parasite where chronic PKDL patients have been implicated in major VL outbreaks in the past. In a series of cross-sectional surveys between 2002-2010, the cumulative incidence of PKDL was estimated at 17% by 5 years in Bangladesh. Most patients had been treated with SSG (95%); the mean interval between VL and PKDL was 19 months. A recent longitudinal study in Fulbaria (2015) of 1918 VL patients with active follow-up showed PKDL rates of 10.2% at 36 months (mean 17.6 months; range 4-43 months) after VL treated with 6 x 5 mg/kg Ambisome® (Koert Ritmeijer, MSF, personal communication). Though VL cases are in decline due to extensive programmes conducted by NKEP, PKDL cases are in the rise and VL:PKDL ratio has risen from 1:0.47 to 1:1.21 from 2016 to 2020. In this current situation, elimination of PKDL cases is of crucial importance in the current VL elimination efforts in Bangladesh as well as in the Indian subcontinent.
2. Knowledge gap: Currently there are no satisfactory treatments for any forms of PKDL. Available treatments include pentavalent antimonial sodium stibogluconate (Pentostam, Stibonate) which have been used since the 1940s. Conventional amphotericin B has been used in India for prolonged periods (60 infusions) but this is impractical and requires careful clinical and biochemical monitoring. Both miltefosine and Ambisome® as monotherapy have shown to be effective. However, with the current recommended scheme there are some drawbacks such as the length of the treatment with miltefosine alone (8-12 weeks), toxicity related to it; a high dose Ambisome® (total dose of 20 mg/kg) given frequently in 4 divided dosage often causes adverse events (e.g. pancytopania, hypokalemia, increased creatinine level etc.). There is also the potential risk for development of resistance with miltefosine as monotherapy. Ivermectin has been proven to have a significant leishmanicidal effect by several experimental studies at higher doses without significant toxicity and may offer shorter duration of treatment thus preventing prolonged hospitalization.
Another possible advantage is reduction of cost. These principles can be applied to PKDL, where the need for an ambulatory treatment with a highly safe, efficacious and user friendly regimen is even more pressing as the patients feel otherwise healthy, except for the rashes.
3. Relevance: This study aims primarily to improve current treatment options. In addition, this will be the first human study ever in PKDL in relation to Ivermectin, in which outcome will be described in clinical, parasitological and immunological terms. Ultimately this study findings will help National Kala-Azar Elimination Program (NKAEP) to adopt specific strategies for elimination of PKDL cases.
Hypothesis (if any): Oral ivermectin in multiple doses is safe and effective for the treatment of PKDL cases.
Objectives: To measure the safety and efficacy of Ivermectin monotherapy regimen (60 mg oral on five consecutive days, for three consecutive months) in treating PKDL patients in Bangladesh.
Methods: This will be a non-control, quasi-experimental, single group, proof of concept, intervention study to assess the safety and efficacy of oral Ivermectin monotherapy (5 x 12 mg daily at a total dose of 60 mg per month for three consecutive months, 180 mg in total) in treating PKDL patients in Bangladesh. In this study we are going to assess whether oral ivermectin in mentioned doses is effective for PKDL treatment or not. All participants will be recruited at SKKRC, Mymensingh with due consent. All patients will be followed up for 6 months since treatment. Cure assessment will be performed. Outcome measures/variables: Safety and efficacy of Ivermectin for PKDL treatment will be determined
Detailed Description:
None
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: