Back to resultsAn Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
Primary Purpose
Visceral Leishmaniasis
Status
Completed
Phase
Not Applicable
Locations
Bangladesh
Study Type
Interventional
Intervention
Paromomycin sulfate
Sponsored by
About this trial
This is an interventional treatment trial for Visceral Leishmaniasis focused on measuring Leishmaniasis, Visceral, kala-azar, Paromomycin, Bangladesh, Injections, Intramuscular, Treatment Outcome, Patient compliance, Medication adherence, Drug toxicity
Eligibility Criteria
Inclusion Criteria:
Signs and symptoms of VL including:
- History of intermittent fever for at least two weeks
- History of weight loss and/or decrease in appetite
- Enlarged spleen
- VL serologically confirmed using the rK39 test:
- Willingness / ability to understand and provide informed consent prior to participation in this study:
- Age ≥ five years and ≤ 55 years, and weighing at least five kg
- Adequately hydrated as assessed by clinical criteria and able to maintain adequate hydration on an outpatient basis through oral intake of fluids
- Clinically stable and appropriate for treatment with PMIM as an outpatient, if possible (subjects may be hospitalized to receive 21-day dosing at the discretion of the investigator)
- Living in the VL-endemic areas in Bangladesh
Exclusion Criteria:
- Active tuberculosis or taking anti-tuberculosis medications
- Previous treatment with Paromomycin IM Injection (PMIM)
- Clinically significant severe anemia as determined by the investigator
- Clinically significant renal or hepatic dysfunction as determined by the investigator, or history of clinically significant renal or hepatic dysfunction
- History of Hepatitis B or C; or known HIV positive
- History of hearing loss
- Other serious illness or medical condition that, in the opinion of the doctor, would interfere with the patient's ability to receive PMIM treatment or comply with the study procedures, or that could obscure toxicity of or response to PMIM
- Major surgery within 30 days prior to first dose of PMIM
- History of hypersensitivity to aminoglycosides or to any of the components of PMIM, including sulfite
- Any history of VL or treatment of VL at any time
- Patients who have received any investigational (unlicensed) drug within the last six months
- Concomitant use of other aminoglycosides (e.g., gentamicin, tobramycin, amikacin), nephrotoxic and ototoxic drugs, or immunosuppressive drugs
- Proteinuria (results > 1+ ) on urine dipstick analysis at screening visit and/or
- Serum creatinine above the upper limit of normal (ie, serum creatinine >1.1 mg/dl in males and >0.9 mg/dl in females
- Pregnant or lactating women
Sites / Locations
- Bhaluka Upazila Health Complex
- Trishal Upazila Health Complex
- Icddr,B
Outcomes
Primary Outcome Measures
Final cure rate
Criteria evaluated (binary fashion):
Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N)
Patient reported resolution of fever and NO fever within the last 5 days? (Y/N)
Spleen size decreased from screening value? (Y/N)
Is the clinical impression of the treating physician that of an adequate clinical response? (Y/N)
The patient is deemed to have achieved final cure if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". In addition, the clinician will inquire about pregnancy status for female patients.
Secondary Outcome Measures
Initial clinical response rate
Criteria evaluated (binary fashion):
Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N)
Patient reported resolution of fever / NO fever within the last 5 days? (Y/N)
Spleen size decreased from screening value? (Y/N)
Is clinical impression of the treating physician that of an adequate clinical response? (Y/N)
The patient is deemed to achieve an initial clinical response if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". Also, the clinician will inquire re: pregnancy status for female patients.
Patient compliance with PMIM treatment
Proportion of patients complying with prescribed 21 daily injections over no more than 22 days.
Safety of PMIM in the study population based on clinical assessment by the study physician at the Upazilla Health Centre.
All serious adverse events (SAEs), regardless of causality, from time of first administration of PMIM through 30 days post-EOT.
All adverse events (AEs), regardless of causality, from time of first dose through 30 days post-EOT.
Vital signs on Study Days 1 to 21/22 (or early termination), any unscheduled visit after EOT, 30 days after EOT, and 6 months after EOT.
Patients who become pregnant during treatment/within 30d following EOT will be included in the safety population. Offspring from pregnancies will be followed for safety under a separate study for a period up to 3 yrs after birth.
To introduce PMIM in government health facilities in rural Bangladesh.
Training study staff to provide treatment with PMIM at selected Upazila level health complexes in rural Bangladesh.
Full Information
NCT ID
NCT01328457
First Posted
January 21, 2011
Last Updated
April 2, 2014
Sponsor
PATH
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh, GVK Biosciences
1. Study Identification
Unique Protocol Identification Number
NCT01328457
Brief Title
An Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
Official Title
An Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh, GVK Biosciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effectiveness of treatment with PMIM in patients with visceral leishmaniasis within the VL-endemic region of Bangladesh at EOT (21/22 days after treatment begins), and at 6 months after end of treatment (Day 202/203, -15 to +30 days).
Detailed Description
Safe, effective and affordable treatments for visceral leishmaniasis (VL) that are widely available to the poorest populations are urgently needed in Bangladesh in areas where the disease is endemic. Paromomycin IM Injection (PMIM) was approved for the treatment of VL in August 2006 by the Drugs Controller General of India (DCGI), and it offers an attractive alternative to treatments that are currently available.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Visceral Leishmaniasis
Keywords
Leishmaniasis, Visceral, kala-azar, Paromomycin, Bangladesh, Injections, Intramuscular, Treatment Outcome, Patient compliance, Medication adherence, Drug toxicity
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Paromomycin sulfate
Other Intervention Name(s)
aminosidin sulfate, aminosidine sulfate, monomycin A sulfate, amminosidin sulfate, catenulin sulfate, crestomycin sulfate, estomycin sulfate, hydroxymycin sulfate, neomycin E sulfate, paucimycin sulfate, Humatin®, Gabbromicina®, Gabromicina®, Gabromycin®, Gabboral®, Kapseal®, Pargonyl
Intervention Description
Paromomycin IM Injection, 11 mg/kg as the base, intramuscular, once a day on 21 consecutive days (or no more than 22 days if one injection is missed during the treatment period).
Primary Outcome Measure Information:
Title
Final cure rate
Description
Criteria evaluated (binary fashion):
Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N)
Patient reported resolution of fever and NO fever within the last 5 days? (Y/N)
Spleen size decreased from screening value? (Y/N)
Is the clinical impression of the treating physician that of an adequate clinical response? (Y/N)
The patient is deemed to have achieved final cure if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". In addition, the clinician will inquire about pregnancy status for female patients.
Time Frame
6 months after end of treatment (Day 202/203, -15 to +30 days)
Secondary Outcome Measure Information:
Title
Initial clinical response rate
Description
Criteria evaluated (binary fashion):
Patient's temperature less than 99.4°F in clinic at EOT visit? (Y/N)
Patient reported resolution of fever / NO fever within the last 5 days? (Y/N)
Spleen size decreased from screening value? (Y/N)
Is clinical impression of the treating physician that of an adequate clinical response? (Y/N)
The patient is deemed to achieve an initial clinical response if answers to a, b, c, AND d are all "Yes" OR if one answer (a, b, or c) is "No" but all others and "d" are "Yes". Also, the clinician will inquire re: pregnancy status for female patients.
Time Frame
End of treatment (21/22 days after treatment begins)
Title
Patient compliance with PMIM treatment
Description
Proportion of patients complying with prescribed 21 daily injections over no more than 22 days.
Time Frame
22 days
Title
Safety of PMIM in the study population based on clinical assessment by the study physician at the Upazilla Health Centre.
Description
All serious adverse events (SAEs), regardless of causality, from time of first administration of PMIM through 30 days post-EOT.
All adverse events (AEs), regardless of causality, from time of first dose through 30 days post-EOT.
Vital signs on Study Days 1 to 21/22 (or early termination), any unscheduled visit after EOT, 30 days after EOT, and 6 months after EOT.
Patients who become pregnant during treatment/within 30d following EOT will be included in the safety population. Offspring from pregnancies will be followed for safety under a separate study for a period up to 3 yrs after birth.
Time Frame
6 months after end of treatment
Title
To introduce PMIM in government health facilities in rural Bangladesh.
Description
Training study staff to provide treatment with PMIM at selected Upazila level health complexes in rural Bangladesh.
Time Frame
October 2011
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signs and symptoms of VL including:
History of intermittent fever for at least two weeks
History of weight loss and/or decrease in appetite
Enlarged spleen
VL serologically confirmed using the rK39 test:
Willingness / ability to understand and provide informed consent prior to participation in this study:
Age ≥ five years and ≤ 55 years, and weighing at least five kg
Adequately hydrated as assessed by clinical criteria and able to maintain adequate hydration on an outpatient basis through oral intake of fluids
Clinically stable and appropriate for treatment with PMIM as an outpatient, if possible (subjects may be hospitalized to receive 21-day dosing at the discretion of the investigator)
Living in the VL-endemic areas in Bangladesh
Exclusion Criteria:
Active tuberculosis or taking anti-tuberculosis medications
Previous treatment with Paromomycin IM Injection (PMIM)
Clinically significant severe anemia as determined by the investigator
Clinically significant renal or hepatic dysfunction as determined by the investigator, or history of clinically significant renal or hepatic dysfunction
History of Hepatitis B or C; or known HIV positive
History of hearing loss
Other serious illness or medical condition that, in the opinion of the doctor, would interfere with the patient's ability to receive PMIM treatment or comply with the study procedures, or that could obscure toxicity of or response to PMIM
Major surgery within 30 days prior to first dose of PMIM
History of hypersensitivity to aminoglycosides or to any of the components of PMIM, including sulfite
Any history of VL or treatment of VL at any time
Patients who have received any investigational (unlicensed) drug within the last six months
Concomitant use of other aminoglycosides (e.g., gentamicin, tobramycin, amikacin), nephrotoxic and ototoxic drugs, or immunosuppressive drugs
Proteinuria (results > 1+ ) on urine dipstick analysis at screening visit and/or
Serum creatinine above the upper limit of normal (ie, serum creatinine >1.1 mg/dl in males and >0.9 mg/dl in females
Pregnant or lactating women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rashidul Haque, MB, PhD
Organizational Affiliation
International Centre for Diarrhoeal Disease Research, Bangladesh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bhaluka Upazila Health Complex
City
Bhaluka
State/Province
Mymensingh District
Country
Bangladesh
Facility Name
Trishal Upazila Health Complex
City
Trishal
State/Province
Mymensingh District
Country
Bangladesh
Facility Name
Icddr,B
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
Citations:
PubMed Identifier
17582067
Citation
Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. N Engl J Med. 2007 Jun 21;356(25):2571-81. doi: 10.1056/NEJMoa066536.
Results Reference
background
PubMed Identifier
9145856
Citation
Kanyok TP, Killian AD, Rodvold KA, Danziger LH. Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects. Antimicrob Agents Chemother. 1997 May;41(5):982-6. doi: 10.1128/AAC.41.5.982.
Results Reference
background
PubMed Identifier
26496648
Citation
Jamil KM, Haque R, Rahman R, Faiz MA, Bhuiyan AT, Kumar A, Hassan SM, Kelly H, Dhalaria P, Kochhar S, Desjeux P, Bhuiyan MA, Khan MM, Ghosh RS. Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh. PLoS Negl Trop Dis. 2015 Oct 23;9(10):e0004118. doi: 10.1371/journal.pntd.0004118. eCollection 2015.
Results Reference
derived
Learn more about this trial
An Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh
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