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

• ClinicalTrials.gov Identifier: NCT03662022
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2018
• Last Update Posted: September 21, 2022
• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: Damien Foundation; Centre d'Infectiologie Charles Mérieux; Fondation Raoul Follereau; Leiden University Medical Center; L'Institut National de la Santé et de la Recherche Médicale; Genoscreen; Instituto Fernandes Figueira
• Information provided by (Responsible Party): Institute of Tropical Medicine, Belgium

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Leprosy	Drug: Rifampicin	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 144000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A cluster randomized trial in which villages are assigned to one of four intervention groups
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar
• Actual Study Start Date: January 2, 2019
• Estimated Primary Completion Date: December 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
No Intervention: No PEP; No PEP will be distributed
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.
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.

Outcome Measures

Primary Outcome Measures :

1. Compare effectiveness in curbing transmission of leprosy of three different approaches of post exposure prophylaxis [ Time Frame: 45 months ]
   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.

Secondary Outcome Measures :

1. Assess cost and feasibility of SDDR-PEP under program conditions [ Time Frame: 45 months ]
   Costs will be calculated per person screened, per person treated with SDDR-PEP and per leprosy case averted.
2. Identify patterns of clustering in transmission of leprosy, allowing better targeting of control measures [ Time Frame: 45 months ]
   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
3. Monitor rifampicin resistance among leprosy patients [ Time Frame: 45 months ]
   We will quantify prevalence of Rifampicin resistant strains of M. leprae on each of the study islands making use of molecular markers
4. Estimate incidence and prevalence of smear positive pulmonary tuberculosis in the study villages [ Time Frame: 45 months ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Comoros

Damien Foundation

Anjouan, Comoros

Damien Foundation

Mohéli, Comoros

Madagascar

Fondation Raoul Follereau

Miandrivazo, Menabe, Madagascar

Sponsors and Collaborators

Institute of Tropical Medicine, Belgium

Damien Foundation

Centre d'Infectiologie Charles Mérieux

Fondation Raoul Follereau

Leiden University Medical Center

L'Institut National de la Santé et de la Recherche Médicale

Genoscreen

Instituto Fernandes Figueira

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Institute of Tropical Medicine, Belgium
• ClinicalTrials.gov Identifier: NCT03662022
• Other Study ID Numbers: 1248/18
• First Posted: September 7, 2018
• Last Update Posted: September 21, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leprosy; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Rifampin; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents; Leprostatic Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; 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