Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202303742093429 Date of Approval: 22/03/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title PEP4LEP + PEP4LEP 2.0 - Chemoprophylaxis for leprosy: comparing the effectiveness and feasibility of a skin camp intervention to a health centre-based intervention
Official scientific title PEP4LEP + PEP4LEP 2.0 - Chemoprophylaxis for leprosy: comparing the effectiveness and feasibility of a skin camp intervention to a health centre based intervention. An implementation trial in Mozambique, Ethiopia and Tanzania
Brief summary describing the background and objectives of the trial This is a two-arm, clustered-randomized implementation trial trial in Mozambique, Ethiopia and Tanzania. The aim of the trial is to contribute to interrupting the transmission of M. leprae by identifying the most effective and feasible method of screening people at risk of developing leprosy and administering chemoprophylaxis in Ethiopia, Mozambique and Tanzania. The primary objectives are: • To compare the effectiveness of a skin camp prophylaxis intervention to a health centre-based prophylaxis intervention in terms of the rate of leprosy patients detected and delay in case detection • To compare the feasibility of the two chemoprophylaxis interventions in terms of cost effectiveness and acceptability • To assess the long-term impact on the case detection delay and new case detection rate of both interventions using mathematical modelling, taking costs into account. The secondary objectives are: • To assess the acceptability of a common skin diseases approach and the use of the NLR SkinApp, a phone application which supports health workers in detecting skin diseases • To compare the capacity of health workers in diagnosing leprosy and other neglected tropical diseases (NTDs) that manifest with skin lesions before the start of the study with their capacity in the the last year in which PEP4LEP 2.0 will be running • To describe the effect of the COVID-19 pandemic on the leprosy case detection delay in PEP4LEP and on leprosy control in general in Ethiopia, Mozambique and Tanzania • To establish lessons learned regarding the organisation of community skin screening events combined with the administration of leprosy chemoprophylaxis • To gain insights in the prevalence of skin NIDs, common skin diseases and HIV/AIDS related skin conditions through both project interventions The project is comparing two interventions for integrated skin screening of contacts of leprosy patients and distribution of single-dose rifampicin as post exposure prophylaxis (SDR-PEP).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PEP4LEP and PEP4LEP2.0
Disease(s) or condition(s) being studied Infections and Infestations,Skin and Connective Tissue Diseases
Sub-Disease(s) or condition(s) being studied leprosy, and other skin diseases including skin NTDs
Purpose of the trial Prevention
Anticipated trial start date 01/10/2018
Actual trial start date 01/10/2018
Anticipated date of last follow up 30/09/2025
Actual Last follow-up date 30/09/2024
Anticipated target sample size (number of participants) 37500
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://bmjopen.bmj.com/content/11/8/e046125
Secondary Ids Issuing authority/Trial register
NTR7503 NL7294 The Dutch Trial Register - Nationaal Trial Register, NTR - is no longer available. Therefore, the NTR data is now merged into The International Clinical Trial Registry Platform - ICTRP.
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Intervention 1 community skin camps ≥15 years: 600 mg rifampicin 10–14 years: 450 mg rifampicin 6–9 years and body weight of ≥20 kg: 300 mg rifampicin ≥2 years old and body weight between 10–20 kg: 150 mg rifampicin single-dose (= 1 day) This intervention is community based, using 1-2 day skin camps set up in the community to screen around 100 contacts (~20 closest household to the index patient) of leprosy patients and provide them with SDR when eligible. 27000
Control Group Intervention 2 health centre based household contact screening ≥15 years: 600 mg rifampicin 10–14 years: 450 mg rifampicin 6–9 years and body weight of ≥20 kg: 300 mg rifampicin ≥2 years old and body weight between 10–20 kg: 150 mg rifampicin single-dose (= 1 day) This is a health centre-based intervention, inviting household contacts to be screened and given SDR when eligible at a health centre. 2430 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Index patients: - Consent to participate in the PEP4LEP project - Diagnosed with leprosy (preferred maximum of 6 months prior to inclusion) - Residence in the PEP4LEP districts for a minimum of 3 months prior to the date of diagnosis - Index patient has started MDT - Community-based skin camp intervention: Leprosy patient gives permission for the set-up of a skin camp in his/her community (sharing their leprosy diagnosis with their contacts is not needed) - Health center-based household screening intervention: Leprosy patient with household contacts, and who is willing to inform these contacts about PEP4LEP Contacts: - Consent to participate in the PEP4LEP project - Community-based skin camp intervention: Community contact of the index patient for a minimum of 3 months - Health center-based household screening intervention: Contact which is a household member of the index patient for a minimum of 3 months, visiting the screening health center =3 months after the index patient was included The eligibility criterium for aditional stakeholders (community leaders, health workers, community health volunteers and health policy decision maker, contacts refusing SDR-PEP) taking part in the acceptability evaluation and the capacity assessment is providing consent to participate in the PEP4LEP project. Index patients: - Index patient or parents/legal guardians unable to understand the purpose and risks of participating in the PEP4LEP study Contacts: - Contact or parents/legal guardians unable to understand the purpose and risks of participating in the PEP4LEP study - Age <2 years and/or <10 kg of weight* - Pregnancy* - Receiving or having received rifampicin for any reason in the last 2 years - Known allergy to rifampicin - History of liver or renal disorders - Individuals with leprosy and those who have possible signs and/or symptoms of leprosy (e.g., leprosy-like skin lesions or nerve manifestations) until their disease status has been clarified** - Individuals with possible signs and/or symptoms of TB (cough for more than two weeks or cough in known HIV/AIDS patients, night sweats, unexplained fever, weight loss) until their disease status has been clarified *** - Individuals with possible signs and/or symptoms of COVID-19 (self-assessed temperature of 38°C or more, respiratory or cold-like symptoms, sudden loss of smell/taste) or possible contact with a COVID-19 patient in the past 14 days*** * A voucher will be given for repeated skin screening and SDR-PEP. This can be used in a PEP4LEP affiliated health center when this person becomes eligible (e.g., after giving birth) ** If referral was needed and no leprosy is detected, repeated skin screening and SDR-PEP can be provided in a PEP4LEP affiliated health center *** Skin screening and SDR-PEP can only be provided in a PEP4LEP affiliated health center after the contact is tested negative for COVID-19/TB (according to national guidelines) 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 2 Year(s) 120 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/02/2020 Ministry of Science and Higher Education Ethiopia National Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
23976 Addis Ababa XQMMWQG Ethiopia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/08/2019 Comite Nacional de Bioetica para Saude Republica de Mozambique Ministerio de Saude
Ethics Committee Address
Street address City Postal code Country
Av Eduardo Mondlane Salvador Allende Maputo 264 Mozambique
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/06/2019 Medical Research Coordinating Committee National Insitute for Medical Research Ministry of Health Community Development Gender Elderly and Children
Ethics Committee Address
Street address City Postal code Country
3 Barack Obama Drive Dar es Salaam 11101 United Republic of Tanzania
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/06/2019 AHRI ALERT Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Jimma Road, ALERT Compound Addis Ababa XPP6562 Ethiopia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • To compare the effectiveness of a skin camp prophylaxis intervention to a health centre-based prophylaxis intervention in terms of the rate of leprosy patients detected and delay in case detection. • To compare the feasibility of the two chemoprophylaxis interventions in terms of cost effectiveness and acceptability. baseline, project end
Secondary Outcome • To assess the acceptability of a common skin diseases approach and the use of the NLR SkinApp, a phone application which supports health workers in detecting skin diseases • To compare the capacity of health workers in diagnosing leprosy and other neglected tropical diseases (NTDs) that manifest with skin lesions before the start of the study with their capacity in the third year baseline, after around 1 and 3 years, project end
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Girawa and Jarso and Midega districts Oromiya region East Hararghe Zone Ethiopia
Meconta and Mogovolas and Murrupula districts Nampula province Nampula Province Mozambique
Lindi and Morogoro and Mvomero Lindi and Morogoro Region Lindi and Morogoro Region United Republic of Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP2 programme under Horizon 2020 Anna van Saksenlaan 51 Den Haag 2593HW Netherlands
Leprosy Research Initiative Wibautstraat 137K Amsterdam 1097DN Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor NLR Wibautstraat 137k Amsterdam 1097DN Netherlands Charities/Societies/Foundation
Secondary Sponsor DAHW Deutsche Lepra und Tuberkulosehilfe eV Raiffeisenstrasse 3 Wurzburg 97080 Germany Charities/Societies/Foundation
Secondary Sponsor Erasmus University Medical Center Rotterdam Dr Molewaterplein 40 Rotterdam 3015GD Netherlands University
COLLABORATORS
Name Street address City Postal code Country
Armauer Hansen Research Institute Jimma Road ALERT Compound Addis Ababa 1005 Ethiopia
Universidade Lurio Bairro de Marrere Nampula V5JXFPJ Mozambique
Catholic University Of Health And Allied Sciences 1464 Mwanza Mwanza 1464 Tanzania
Ministry of Health Ethiopia 1234 Sudan Street Addis Ababa Ethiopia
Ministry of Health Mozambique Avenida Eduardo Mondlane Maputo 2HJP972 Mozambique
National TB and Leprosy Programme of Ministry of Health Community Development Gender Elderly and Children United Republic of Tanzania Wizara ya Afya Dodoma United Republic of Tanzania
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Liesbeth Mieras l.mieras@nlrinternational.org 31205950500 Wibautstraat 137k
City Postal code Country Position/Affiliation
Amsterdam Netherlands NLR
Role Name Email Phone Street address
Public Enquiries Anne Schoenmakers a.schoenmakers@nlrinternational.org 31205950500 Wibautstraat 137k
City Postal code Country Position/Affiliation
Amsterdam Netherlands NLR
Role Name Email Phone Street address
Scientific Enquiries Thomas Hambridge t.hambridge@erasmusmc.nl +31107040704 Dr Molewaterplein 40
City Postal code Country Position/Affiliation
Rotterdam Netherlands Erasmus University Medical Center
Role Name Email Phone Street address
Principal Investigator Kidist Bobosha kidist.bobosha@ahri.gov.et 251113471614 Jimma Road ALERT Campus
City Postal code Country Position/Affiliation
Addis Ababa 1005 Ethiopia PI Ethiopia AHRI
Role Name Email Phone Street address
Principal Investigator Francisco Mitano fernando.mitano@alumni.usp.br 25826212425 Governo do Distrito de Nampula
City Postal code Country Position/Affiliation
Nampula Mozambique PI Mozambique MoH
Role Name Email Phone Street address
Principal Investigator Beatrice Mutayoba beatricemutayoba@ntlp.go.tz 2550262960150 NTLP PO 743
City Postal code Country Position/Affiliation
Dodoma 743 United Republic of Tanzania PI Tanzania NTLP
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes PEP4LEP is committed to sharing individual participant data (IPD) with qualified researchers and institutions for future data analysis and study replication. A data management plan was developed, consistent with EU regulation 536/2014 for clinical medication-related research projects. Quantitative data collected is recorded paper-based and entered into the Research Electronic Data Capture (REDCap) system. REDCap is linked to a centralised database server hosted by Erasmus MC. Access to national virtual servers (Ethiopia, Mozambique, Tanzania) is limited to those authorized by institutional research coordinators. Hard copy data are maintained at field sites in secure locations, and for backup and analysis purposes securely transferred from the national virtual server by accessing a virtual machine hosted by Erasmus MC and cut-off from the internet. To ensure privacy and confidentiality, a data pseudonymisation system (participant ID codes) is in place, and personal identifiers (i.e. names) are not entered in the national virtual server or centralised database. Project staff are trained in privacy and confidentiality. Restricted access to the database is implemented using a secure system to prevent unauthorised access. Qualitative data collected in the supporting studies are kept confidential. Interviews, observations, and focus group data are reported only by generic identifying characteristics, (i.e. age). Standards for data storage include security (i.e. antivirus/firewalls), regular backups, easy access for authorized users and measures to prevent theft of tablets/laptops/desktops. Used Individual patient data (IPD) Sharing Statement in accordance with WHO guidelines: “All collected data are confidential. Your name is only known by people directly involved in this study. The results of the study may be published, but no names or identifying pictures of individuals are used without prior explicit consent.” Also see both websites listed below. Informed Consent Form,Study Protocol PEP4LEP study data will be stored for 25 years according to EU regulation 536/2014 considering clinical medication-related research projects. Sharing data and study materials, as well as open access publishing, are important values of the EU research and innovation program Horizon 2020, the European and Developing Countries Clinical Trials Partnership (EDCTP), and the PEP4LEP consortium. Study outcomes are expected to be relevant for other sub-Saharan countries and leprosy endemic areas outside the African context. Results will be shared open access via peer-reviewed journals, conferences, and platforms such as Infolep and infoNTD. Communities affected and local and national policymakers will be informed on the study outcomes via community meetings/workshops. In addition, project recommendations will be offered to all relevant authorities in Ethiopia, Mozambique, and Tanzania. The uptake of SDR-PEP into national leprosy guidelines is (already) advised by the World Health Organization (WHO). Qualified researchers and institutions who are interested in accessing the PEP4LEP IPD should contact the data custodian at Erasmus MC. All requests will be reviewed and access will be granted in accordance with the study's data sharing policies and procedures.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://url1.io/s/Vv8Ek & https://trialsearch.who.int/Trial2.aspx?TrialID=NTR7503 No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information