Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study

NCT01360762 | Completed Phase 3 Results DMC

• 1 other identifier: ITMC0109
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 3

Brief Summary

Visceral leishmaniosis (VL) is widely reported in Ethiopia, with about 30% of cases being associated with human immunodeficiency virus (HIV). In absence of antiretroviral treatment (ART), poor prognosis, high mortality and high relapse rates are characteristic of Ethiopian VL patients with HIV co-infection. Conversely, co-infection can be successfully managed via a combination of effective treatment of the initial episode, timely ART and prevention of relapses. Actually, until cellular immunity returns with ART, the patient is at risk of VL relapses, which can result in death, severe illness, reduced ART efficacy, drug-resistance and possibly transmission of drug-resistant Leishmania donovani. Patients most vulnerable to relapses are those with high levels of immunosuppression, with previous VL episodes, or with opportunistic infections (OIs). The most important factor to prevent relapses seems to be the clearance of visible parasites. Limited studies in Europe show that HIV co-infected patients may benefit from secondary prevention with antimonials (part of mainstay treatment for VL in Ethiopia) and pentamidine (PM), not used for VL treatment in Africa. Such maintenance treatment has not been studied in African VL, but the poor outcomes without secondary prevention highlight a need of better care to patients at risk of relapse. This prospective cohort study aims at documenting the patient's outcomes of secondary prophylaxis with PM in VL-HIV co-infection, in terms of time to relapse or death, safety and feasibility, before it can be considered for general use in Ethiopia. A placebo group is not included, due to the clear advantages of the intervention to the patient population.

Conditions

Visceral Leishmaniosis; HIV-infection/Aids

Keywords

Secondary prophylaxis; Visceral leishmaniasis; Relapses; HIV co-infection; Pentamidine; Ethiopia

Outcome Measures

Primary Outcomes (2)

• Probability of Relapse-free Survival

  Probability of relapse-free survival up to one year after the start of the intervention (PSP) (at month 6 and month 12)

  up to 1 year after the start of the intervention (PSP)

• Number of Participants With Serious Adverse Events (SAEs)

  Number of patients with SAEs which are possibly, probably or definitely drug-related following clinician's assessment or that lead to permanent drug discontinuations during the first year of pentamidine administration

  1 year

Secondary Outcomes (3)

• Number of Participants With Adverse Events

  1 year

• Number of Treatment Discontinuations and Interruptions

  30 months

• Number of Required Additional Interventions

  30 months

Study Arms (1)

Pentamidine Secondary Prophylaxis (PSP)

EXPERIMENTAL

Patients with co-infection of human immunodeficiency virus (HIV)and visceral leishmaniosis (VL), having being treated for VL, are allocated to pentamidine secondary prophylaxis, to prevent VL relapses. The treatment period is of 12 months, plus an "extended treatment period" of 0 to 6 months depending on the immunosuppression status, plus 12 months follow-up after the extended treatment period.

Drug: Pentamidine

Interventions

Pentamidine DRUG

Pentamidine isethionate 300 mg for one vial for intramuscular or intravenous route(1 mg of pentamidine isethionate is equivalent to 0.57 mg of pentamidine base)

Also known as: PENTACARINAT 300 mg, by Sanofi-Aventis

Pentamidine Secondary Prophylaxis (PSP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with Visceral Leishmaniosis (VL) during the recruitment period that are EITHER treated for VL relapse and have a documented negative test of cure (TOC), OR are treated for primary VL and have a documented CD4 \<200 or WHO stage 4 disease during the recruitment period and have a documented negative TOC
• Patients treated for VL in the past with documented CD4 \<200 or WHO stage 4 disease during the recruitment period AND documented negative TOC after the latest VL treatment and currently asymptomatic OR currently negative diagnostic test (microscopy)
• Patients agreeing to start or continue antiretroviral treatment (first or second line)
• Patients willing to provide written informed consent

You may not qualify if:

• Patients with known hypersensitivity to pentamidine
• Patients with known renal failure
• Patients with diabetes mellitus (type I or II)
• Patients unlikely to attend follow-up visits/comply with study requirements
• Pregnant and lactating women
• Any other condition that could increase the risk of toxicity of pentamidine to such an extent outweighing the expected benefit (eg severe cardiac dysfunction).

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Addis Ababa University: collaborator
• University of Gondar: collaborator
• Tigray Regional Health Bureau, Tigray Region: collaborator
• Amhara Regional Health Bureau, Amhara Region: collaborator
• Medecins Sans Frontieres, Netherlands: collaborator
• Leishmania East Africa Platform (LEAP): collaborator
• Drugs for Neglected Diseases: collaborator

Study Sites (3)

Abdurafi Health Center/Médecins Sans Frontières

Abdurafi, Amhara, Ethiopia

Location

Kahsay Abera Hospital

Humera, Tigray, Ethiopia

Location

Leismania Research and Treatment Centre, University of Gondar Hospital

Gonder, Ethiopia

Location

Related Publications (1)

• Diro E, Ritmeijer K, Boelaert M, Alves F, Mohammed R, Abongomera C, Ravinetto R, De Crop M, Fikre H, Adera C, van Loen H, Tsoumanis A, Adriaensen W, Hailu A, Griensven JV. Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus-Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial. Clin Infect Dis. 2018 Jan 18;66(3):444-451. doi: 10.1093/cid/cix807.

  PMID: 29020217 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Leishmaniasis, Visceral; Recurrence

Interventions

Pentamidine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Vector Borne Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Johan Van Griensven
• Organization: Institute of Tropical Medicine Antwerp

jvangriensven@itg.be

+32(0)32476426

Study Officials

• Ermias Diro, MD

  University of Gondar, Ethiopia

  STUDY DIRECTOR

• Johan Van Griensven, MD, PhD

  ITM

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: May 26, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 15, 2019
• Results First Posted: February 15, 2019

Record last verified: 2018-10

Locations

ET (3)