| CTRI Number |
CTRI/2010/091/000159 [Registered on: 23/02/2010] |
| Last Modified On: |
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| Post Graduate Thesis |
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| Type of Trial |
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Type of Study
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| Study Design |
Single Arm Study |
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Public Title of Study
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Safety and efficacy of liposomal amphotericin B (Ambisome) in patients with post kala-azar dermal leishmaniasis(PKDL). |
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Scientific Title of Study
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"Safety and efficacy of liposomal amphotericin B (Ambisome) in patients with post kala-azar dermal leishmaniasis(PKDL)". |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| PKDL_18_RMRI-MSF |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
Dr.Prabhat Kumar Sinha |
| Designation |
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| Affiliation |
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| Address |
RMRIMS(ICMR),Agam Kuan.
Clinical Medicine,RMRIMS.
Patna
BIHAR
800007
India |
| Phone |
06122635456 |
| Fax |
0612 2634379 |
| Email |
pksinha18@yahoo.com |
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Details of Contact Person
Scientific Query
|
| Name |
Dr.Prabhat Kumar Sinha |
| Designation |
|
| Affiliation |
Indian Council of Medical Research. |
| Address |
RMRIMS(ICMR),Agam Kuan.
Clinical Medicine,RMRIMS.
Patna
BIHAR
800007
India |
| Phone |
06122635456 |
| Fax |
0612 2634379 |
| Email |
pksinha18@yahoo.com |
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Details of Contact Person
Public Query
|
| Name |
Dr.Prabhat Kumar Sinha |
| Designation |
|
| Affiliation |
|
| Address |
RMRIMS(ICMR),Agam Kuan.
Clinical Medicine,RMRIMS.
Patna
BIHAR
800007
India |
| Phone |
06122635456 |
| Fax |
0612 2634379 |
| Email |
pksinha18@yahoo.com |
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Source of Monetary or Material Support
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| Material Support: Ambisome to be provided by MSF,Spain |
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Primary Sponsor
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| Name |
RMRIMS(ICMR). |
| Address |
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| Type of Sponsor |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
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Sites of Study
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| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr.P.K.Sinha |
RMRIMS(ICMR) |
RMRIMS(ICMR),Agam Kuan.,Clinical Medicine,RMRIMS(ICMR)-800007
Patna
BIHAR |
06122635456
0612 2635456
pksinha18@yahoo.com |
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Details of Ethics Committee
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| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee,RMRIMS(ICMR) |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
In India 5 to 10 % of patients with visceral leishmaniasis (VL) go on to develop post kala azar dermal leishmaniasis (PKDL, three months to three years after VL has been apparently cured. Indian PKDL can occur concurrently with VL also as reported in a few patients.Clinical features consist of hypopigmented macules and/or diffuse infiltration, papules, nodules, or plaques.The current treatment recommendations for treatment include either sodium stibogluconate 20 mg/kg intramusclualry (10 ml for a 50 kg person) for 120 days or amphotericin B deoxycholate infusions 20 infusions for three such courses over an eighty day period. Such prolonged, painful and toxic regimen results in frequent non-compliance, which is almost a rule. Thus, treating PKDL has been an exceptionally difficult task. Unless there are compelling situation like lesions over face preventing marriage, patients tend to avoid treatment.
Patients with PKDL represent an important but largely neglected reservoir of infection that perpetuates anthroponotic Leishmania donovani disease in India, and focal VL outbreaks have been linked to an index case of PKDL.
Ambisome is a liposomal formulation of amphotericin B, associated with significantly lower renal toxicity than amphotericin B, which is dose-limiting. It is an effective and well tolerated drug licensed for treatment of VL in India.
AmBisome is the safest and probably the most efficacious of all anti-leishmanial drugs currently available. (Bern et al, 2006).A drug which is safe and effective after parentral administration for shorter duration is needed for the treatment of patients with post kala azar dermal leishmaniasis. Such drug would facilitate treatment, increase compliance, and lower cost of treatment.
The proposed trial objectives are:
Primary objective:
? To assess liposomal amphotericin B regimens 2.5 mg/kg/bw for 20 consecutive days duration for their curative potential in PKDL (parameter: rate of patients with macular/nodular and papular lesions who achieve negative parasitology and clinical severity score of zero 12 months after end of treatment).
Secondary objectives:
? To characterize the safety of liposomal amphotericin B when used for periods up to 20 days in three courses at the interval of 15 to 30 days.
? To assess the rates of initial response in relation to duration of treatment.
? To assess the rates of relapse after initial response
? To assess the clinical response of facial erythema and mucosal lesions
Total number of patients planned 50.
Duration of study: two years.
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
Liposomal Amphotericin B |
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| Comparator Agent |
NIL |
N/A |
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Inclusion Criteria
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| Age From |
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| Age To |
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| Gender |
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| Details |
Inclusion criteria:
? Male or female patient aged 5 years or older
? Post kala azar dermal leishmaniasis (PKDL), parasitologically confirmed (amastigotes in slit-skin or snip skin smears and/or skin biopsies)
? Nodules, papules or plaques as clinical signs consistent with post kala azar dermal leishmaniasis.
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| ExclusionCriteria |
| Details |
Exclusion criteria:
Safety concerns:
? Thrombocyte count <100 x 109/l
? Leukocyte count <1.5 x 109/l
? Hemoglobin < 5.0 g/100 ml
? ASAT, ALAT, AP >3 times upper limit of normal range
? Bilirubin >2 times upper limit of normal range
? Serum creatinine or BUN >1.5 times upper limit of normal range
? Major surgery within last 2 weeks
? Any non-compensated or uncontrolled condition, such as active tuberculosis, malignant disease, severe malaria, HIV, or other major infectious diseases
Lack of suitability for the trial:
? Concomitant treatment with other anti-leishmaniasis drugs
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
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Not Applicable |
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Blinding/Masking
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Not Applicable |
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Primary Outcome
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| Outcome |
TimePoints |
| Efficacy variable:Presence of parasites in slit-skin or skin snip smears.
Safety variables: - Vital parameters
? Laboratory (hemogram, clinical chemistry)
8.6 Assessments after 12 months follow up
Efficacy variable: - Presence of parasites in slit-skin or snip skin smears, skin biopsy
Clinical picture of papules, nodules and plaques
Safety variables: - Vital parameters
? Laboratory (hemogram, clinical chemistry)
Overall assessment: - Study outcome / response to therapy
For the rates of definite and apparent cures 95%-lower confidence bounds will be calculated. The primary analysis will be based on the intent to treat population. |
Assessments after 12 months follow up:
Efficacy variable: - Presence of parasites in slit-skin or snip skin smears, skin biopsy
- Clinical picture of papules, nodules and plaques
Safety variables: - Vital parameters
? Laboratory (hemogram, clinical chemistry)
Overall assessment: - Study outcome / response to therapy
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Secondary Outcome
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| Outcome |
TimePoints |
| Disappearnce of clinical picture of papules, nodules and plaques. |
12 months |
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Target Sample Size
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Total Sample Size="50"
Sample Size from India=""
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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N/A |
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Date of First Enrollment (India)
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Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
18/02/2010 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
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Years="2"
Months="0"
Days="0" |
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Recruitment Status of Trial (Global)
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Open to Recruitment |
| Recruitment Status of Trial (India) |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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This is open label stidy to assess the efficacy and safety of liposomal amphotericin B regimens 2.5 mg/kg/bw for 20 consecutive days duration for their curative potential in PKDL (parameter: rate of patients with macular/nodular and papular lesions who achieve negative parasitology and clinical severity score of zero 12 months after end of treatment).
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