Clinical trial NCT01328457: 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
Overall status: COMPLETED
Phase: NA
Conditions: Visceral Leishmaniasis
Keywords: Leishmaniasis, Visceral
kala-azar
Paromomycin
Bangladesh
Injections, Intramuscular
Treatment Outcome
Patient compliance
Medication adherence
Drug toxicity
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh
name: GVK Biosciences
First posted: 2011-04-04
Enrollment: 120
Sex: ALL
Minimum age (years): 5
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. VL serologically confirmed using the rK39 test:
3. Willingness / ability to understand and provide informed consent prior to participation in this study:
4. Age ≥ five years and ≤ 55 years, and weighing at least five kg
5. Adequately hydrated as assessed by clinical criteria and able to maintain adequate hydration on an outpatient basis through oral intake of fluids
6. 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)
7. Living in the VL-endemic areas in Bangladesh

Exclusion Criteria:

1. Active tuberculosis or taking anti-tuberculosis medications
2. Previous treatment with Paromomycin IM Injection (PMIM)
3. Clinically significant severe anemia as determined by the investigator
4. Clinically significant renal or hepatic dysfunction as determined by the investigator, or history of clinically significant renal or hepatic dysfunction
5. History of Hepatitis B or C; or known HIV positive
6. History of hearing loss
7. 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
8. Major surgery within 30 days prior to first dose of PMIM
9. History of hypersensitivity to aminoglycosides or to any of the components of PMIM, including sulfite
10. Any history of VL or treatment of VL at any time
11. Patients who have received any investigational (unlicensed) drug within the last six months
12. Concomitant use of other aminoglycosides (e.g., gentamicin, tobramycin, amikacin), nephrotoxic and ototoxic drugs, or immunosuppressive drugs
13. Proteinuria (results \> 1+ ) on urine dipstick analysis at screening visit and/or
14. Serum creatinine above the upper limit of normal (ie, serum creatinine \>1.1 mg/dl in males and \>0.9 mg/dl in females
15. Pregnant or lactating women

Primary outcomes:
measure: Final cure rate
timeFrame: 6 months after end of treatment (Day 202/203, -15 to +30 days)
Secondary outcomes:
measure: Initial clinical response rate
timeFrame: End of treatment (21/22 days after treatment begins)
measure: Patient compliance with PMIM treatment
timeFrame: 22 days
measure: Safety of PMIM in the study population based on clinical assessment by the study physician at the Upazilla Health Centre.
timeFrame: 6 months after end of treatment
measure: To introduce PMIM in government health facilities in rural Bangladesh.
timeFrame: October 2011
Other outcomes:
Locations:
city: Bhaluka
country: Bangladesh
facility: Bhaluka Upazila Health Complex
state: Mymensingh District
city: Trishal
country: Bangladesh
facility: Trishal Upazila Health Complex
state: Mymensingh District
city: Dhaka
country: Bangladesh
facility: Icddr,B
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Rashidul Haque, MB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.