Ignite Creation Date:
2024-05-05 @ 11:40 PM
Last Modification Date:
2024-10-26 @ 10:37 AM
Study NCT ID:
NCT01380314
Status:
COMPLETED
Last Update Posted:
2011-06-27
First Post:
2008-05-07
Brief Title:
Oral Miltefosine Plus Topical Imiquimod to Treat Cutaneous Leishmaniasis
Sponsor:
Foundation Fader
Organization:
Foundation Fader
Study Overview
Official Title:
Treatment of Bolivian Cutaneous Leishmaniasis With a Combination of Oral Miltefosine Plus Topical Imiquimod 5
Status:
COMPLETED
Status Verified Date:
2011-06
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:
Cutaneous leishmaniasis is endemic in the New World from approximately the US-Mexican border through Central America and the Northern part of South America down to the level of Rio de Janeiro
Until recently the standard treatment for the leishmaniases was pentavalent antimony Glucantime or Pentostam The cure rate for L panamensis in Colombia is 91-93 Soto 1993 Velez 1997 a large study with several formulations of antimony found a combined Bolivia-Colombia cure rate of 86 Soto 2004b and in work just completed the cure rate in Palos Blancos Bolivia is 15 of 16 94 Soto manuscript in preparation Nevertheless pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity gastrointestinal complaints liver enzyme elevations pancreatic enzyme elevations all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis
The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia In Colombia the cure rate for miltefosine was 91 Soto 2004a and in the just-completed trial in Palos Blancos the cure rate for miltefosine was 32 of 37 88 Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25 of patients and low-grade elevation of creatinine also in approximately 25 of patients Soto 2001 Soto 2004
The 6-month cure rate did not reach 100 and miltefosine was relatively slow to cure compared to Sb 31 of 44 evaluable miltefosine patients 70 were cured by 1 month after therapy compared to 16 of 16 evaluable Glucantime patients 100
Imiquimod Aldara 3M Pharmaceuticals is a novel immune response-activating compound approved by the FDA for cervical warts that activates macrophage killing of Leishmania species Combined imiquimod plus Glucantime was used as rescue treatment in 12 patients with Peruvian cutaneous leishmaniasis who had previously not responded to Glucantime alone 90 of patients were cured at the 6-month follow-up period Arevalo 2001 In a follow up study Miranda-Verastegui et al 2005 naïve patients were randomized between the combination of Sb plus imiquimod 18 patients vs Sb plus placebo 20 patients The cure rate at 1 month after therapy was 50 in the imiquimod Sb group compared to 15 in the placeboSb group p 002 By 12 months after therapy the Sbplacebo group had caught up and the cure rate was 72-75 in each group Local side effects were evaluated Edema itching burning pain were equal in the two groups There was more erythema in the imiquimod grup 55 of patients compared to the placebo group 25 of patients
The Imiquimod studies in neighboring Peru suggest that combination with this immunomodulator is capable of decreasing the time to cure and potentially increasing the cure rate in Andean cutaneous leishmaniasis The present study will evaluate the combination of oral miltefosine plus topical imiquimod for cutaneous leishmaniasis in Bolivia If in the first group of patients cure rate at 1 month after therapy is appreciably above the 70 historic value for miltefosine alone and the cure rate at 6 months is greater than the 88 historic value for miltefosine alone subsequent patients will be randomized between miltefosineimiquimod and miltefosineplacebo cream
Until recently the standard treatment for the leishmaniases was pentavalent antimony Glucantime or Pentostam The cure rate for L panamensis in Colombia is 91-93 Soto 1993 Velez 1997 a large study with several formulations of antimony found a combined Bolivia-Colombia cure rate of 86 Soto 2004b and in work just completed the cure rate in Palos Blancos Bolivia is 15 of 16 94 Soto manuscript in preparation Nevertheless pentavalent antimonials have the disadvantages of multiple injections and mild-moderate clinical toxicity gastrointestinal complaints liver enzyme elevations pancreatic enzyme elevations all of which are particularly unpleasant for a moderate clinical problem such as cutaneous leishmaniasis
The oral agent Miltefosine has now been shown to be as effective as antimony in Colombia and Bolivia In Colombia the cure rate for miltefosine was 91 Soto 2004a and in the just-completed trial in Palos Blancos the cure rate for miltefosine was 32 of 37 88 Side effects seen in patients with cutaneous disease that can be specifically attributed to the drug are nausea and vomiting of mild grade in approximately 25 of patients and low-grade elevation of creatinine also in approximately 25 of patients Soto 2001 Soto 2004
The 6-month cure rate did not reach 100 and miltefosine was relatively slow to cure compared to Sb 31 of 44 evaluable miltefosine patients 70 were cured by 1 month after therapy compared to 16 of 16 evaluable Glucantime patients 100
Imiquimod Aldara 3M Pharmaceuticals is a novel immune response-activating compound approved by the FDA for cervical warts that activates macrophage killing of Leishmania species Combined imiquimod plus Glucantime was used as rescue treatment in 12 patients with Peruvian cutaneous leishmaniasis who had previously not responded to Glucantime alone 90 of patients were cured at the 6-month follow-up period Arevalo 2001 In a follow up study Miranda-Verastegui et al 2005 naïve patients were randomized between the combination of Sb plus imiquimod 18 patients vs Sb plus placebo 20 patients The cure rate at 1 month after therapy was 50 in the imiquimod Sb group compared to 15 in the placeboSb group p 002 By 12 months after therapy the Sbplacebo group had caught up and the cure rate was 72-75 in each group Local side effects were evaluated Edema itching burning pain were equal in the two groups There was more erythema in the imiquimod grup 55 of patients compared to the placebo group 25 of patients
The Imiquimod studies in neighboring Peru suggest that combination with this immunomodulator is capable of decreasing the time to cure and potentially increasing the cure rate in Andean cutaneous leishmaniasis The present study will evaluate the combination of oral miltefosine plus topical imiquimod for cutaneous leishmaniasis in Bolivia If in the first group of patients cure rate at 1 month after therapy is appreciably above the 70 historic value for miltefosine alone and the cure rate at 6 months is greater than the 88 historic value for miltefosine alone subsequent patients will be randomized between miltefosineimiquimod and miltefosineplacebo cream
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None