Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar (PEOPLE)

This is a cluster randomized trial on effectiveness of different modalities of Single Double Dose of Rifampicin Post-Exposure Prophylaxis (SDDR-PEP) for leprosy in the Comoros (Anjouan and Mohéli) and Madagascar.

The study aims to identify which approach to the selection of contacts for post exposure prophylaxis is most effective to reduce incident leprosy, and to Interrupt ongoing transmission from asymptomatic persons in the process of developing multibacillary leprosy.

Study Overview

• Status: Completed
• Conditions: Leprosy
• Intervention / Treatment: Drug: Rifampicin

Detailed Description

For the purpose of the study, villages on the Comoros and Madagascar that will be randomly assigned to one of the study arms, will be screened on a yearly basis for 4 consecutive years. Depending on which of the 4 arms a village is assigned to, people in the surroundings of a leprosy patient will or will not be offered Post-Exposure Prophylaxis (PEP) using rifampicin at 20mg/kg single dose:

1. No Post-Exposure Prophylaxis (PEP) is given to anyone
2. PEP is given to all household contacts of incident leprosy cases
3. PEP is given to all people who live in a 100m radius of incident leprosy cases
4. PEP is given to all household contacts of incident leprosy cases as well as to all others who live within a 100m radius of an incident leprosy case and test positive in the UCP-LFA detecting anti-M. leprae PGL-I IgM antibodies (Ab) in fingerstick blood (anti-PGL-1)

• Study Type: Interventional
• Enrollment (Actual): 144000
• Phase: Phase 3

Contacts and Locations

Study Locations

• Comoros
  • Anjouan, Comoros
    • Damien Foundation
  • Mohéli, Comoros
    • Damien Foundation
• Madagascar
  • Menabe
    • Miandrivazo, Menabe, Madagascar
      • Fondation Raoul Follereau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Living in one of the study villages
• Aged 2 years and above
• Able and willing to provide informed consent

Exclusion Criteria:

• Signs of active leprosy (*)
• Signs of active pulmonary tuberculosis (cough ≥2 weeks duration) (*)
• Having received Rifampicin within the last 24 months (*)

(*) These people may still be included for yearly leprosy screening, but will be excluded to receive PEP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No PEP; No PEP will be distributed
Other: Household PEP; PEP will be given to all household contacts of an incident leprosy patient	Drug: Rifampicin; Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.
Experimental: PEP 100m; PEP will be given to all household contacts of leprosy patients and to all other people living within a 100m radius of an incident leprosy patient.	Drug: Rifampicin; Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.
Other: PEP 100m + positive for anti-PGL-I IgM Ab; PEP will be given to all household contacts of leprosy patients and to all other people living within a 100m radius of an incident leprosy patient who test positive in the UCP-LFA detecting anti-M. leprae PGL-I IgM Ab in fingerstick blood (anti-PGL-I)	Drug: Rifampicin; Rifampicin will be given in the same way to arms 2, 3 and 4 (weight dependent). Only the strategy of whom to offer PEP differs between the arms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Effectiveness in Curbing Transmission of Leprosy of Three Different Approaches of Post Exposure Prophylaxis	leprosy number of new cases per 1000 person years is reported. Incident cases were cases newly diagnosed while under follow-up. In the statisical analysis table: three incidence rate ratios between the comparator arm (arm 1) and each of the three intervention arms. These ratios will be based on incidence rates measured between the first and fourth household survey in each of the intervention arms, always divided by that of the comparator arm. Please note that accross the years a part of the same participants are revisited again, which might explain discrepancies in the overall number of participants analyzed.	45 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess cost and feasibility of SDDR-PEP under program conditions	Costs will be calculated per person screened, per person treated with SDDR-PEP and per leprosy case averted.	45 months
Identify patterns of clustering in transmission of leprosy, allowing better targeting of control measures	We will quantify the degree of clustering as the average proportion of leprosy cases belonging to a same phylogenetic cluster by village. Geographic clustering will also be assessed by calculating risk ratios for being diagnosed with leprosy as a function of geographic distance from incident cases diagnosed earlier in each of the four arms	45 months
Monitor rifampicin resistance among leprosy patients	We will quantify prevalence of Rifampicin resistant strains of M. leprae on each of the study islands making use of molecular markers	45 months
Estimate incidence and prevalence of smear positive pulmonary tuberculosis in the study villages	During door-to-door surveys for leprosy we will enquire about chronic cough and screen for pulmonary tuberculosis if indicated. Prevalence of pulmonary tuberculosis will be calculated per island based on the results of the baseline survey, using as denominator the total population screened on the island. After each survey round annual incidence rates will be calculated based on the results of the follow-up surveys	45 months

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: Leiden University Medical Center; Damien Foundation; Instituto Fernandes Figueira; Genoscreen; Fondation Raoul Follereau; Centre d'Infectiologie Charles Mérieux; L'Institut National de la Santé et de la Recherche Médicale
• Investigators: Study Chair: Bouke de Jong, MD, PhD, Institute of Tropical Medicine; Study Director: Epco Hasker, MD, Institute of Tropical Medicine; Principal Investigator: Younoussa Assoumani, MD, Damien Foundation; Principal Investigator: Bertrand Cauchoix, MD, Fondation Raoul Follereau

Publications and helpful links

General Publications

• Ortuno-Gutierrez N, Younoussa A, Randrianantoandro A, Braet S, Cauchoix B, Ramboarina S, Baco A, Mzembaba A, Salim Z, Amidy M, Grillone S, Richardus JH, de Jong BC, Hasker E. Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): a cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts. BMC Infect Dis. 2019 Dec 5;19(1):1033. doi: 10.1186/s12879-019-4649-0.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Leprosy; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; Rifampin
• Other Study ID Numbers: 1248/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No