Phase 3
N=74
Prophylaxis of Visceral Leishmaniasis Relapses in HIV Co-infected Patients With Pentamidine: a Cohort Study
Visceral Leishmaniosis · HIV-infection/Aids
Bottom Line
View on ClinicalTrials.gov: NCT01360762 ↗Enrolled (actual)
74
Serious AEs
44.6%
Results posted
Feb 2019
Primary outcome: Primary: Probability of Relapse-free Survival — 79; 71 percentage probability
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pentamidine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Institute of Tropical Medicine, Belgium
- Primary completion
- Nov 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Probability of Relapse-free Survival |
79; 71 | — |
| PRIMARY Number of Participants With Serious Adverse Events (SAEs) |
3 | — |
| SECONDARY Number of Participants With Adverse Events |
30; 17 | — |
| SECONDARY Number of Treatment Discontinuations and Interruptions |
2; 4; 0 | — |
| SECONDARY Number of Required Additional Interventions |
10; 2; 2; 1 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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).
Data sourced from ClinicalTrials.gov (NCT01360762). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.