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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201703002069220 Date of Registration: 02/03/2017
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A comparison of reactive case detection and focal mass drug administration strategies in the Central Highlands areas of Madagascar
Official scientific title A comparison of reactive case detection and focal mass drug administration strategies to inform the national malaria control strategy toward elimination. Cluster Randomized Trial in 14 districts in the Central Highlands areas of Madagascar
Brief summary describing the background and objectives of the trial The Central Highlands of Madagascar represent an area of low and unstable malaria transmission prone to malaria epidemics. The latest Malaria Indicator Surveys (MIS) show that in 2011 and 2013 malaria prevalence by microscopy was respectively 0.8% and 0.7% in the Central Highlands among children under five years (1). Both levels are low enough to suggest this region of Madagascar is in a pre-elimination phase. However, successive malaria control interventions also lead to a complex epidemiological pattern with clustering in small geographical areas or in subpopulations. Reactive Case Detection (RCD) is proposed to detect and treat malaria cases in areas of low endemicity. RCD describes an activity in which community members within a given radius are screened and treated around a passively detected index case, who presents to a health center (HC). A related strategy to RCD is focal or reactive mass drug administration (fMDA), whereby community members around an index case are treated with an antimalarial regardless of testing or test result. Since malaria rapid diagnostic tests (RDTs) used in RCD are not able to reliably detect low-density parasite infections, they might miss sub-microscopic malaria infections that can continue to transmit the parasite. The objective of this study is to test the effectiveness of reactive case detection (RCD) and focal mass drug administration (fMDA) for reducing malaria transmission. The study will assess the effectiveness of screening and treating community members around an index case (RCD) as well as administering an antimalarial to all households around an index case (fMDA). In order to assess the effectiveness of interventions, the annual parasite incidence (API) will be estimated through an enhanced malaria surveillance system at both community (CHV) and HC level. Concurrently, to estimate changes in the parasite reservoir, a ¿Malaria PCR Prevalence Population¿ survey will be conducted annually.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) RCD
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 27/03/2017
Actual trial start date 21/08/2017
Anticipated date of last follow up 31/03/2019
Actual Last follow-up date 20/10/2017
Anticipated target sample size (number of participants) 195000
Actual target sample size (number of participants) 2077
Recruitment status Suspended
Publication URL
Secondary Ids Issuing authority/Trial register
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
Parallel: different groups receive different interventions at same time during study Randomised Computer generated Cluster randomization for 39 clusters Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Reactive Case detection ASAQ once a day and primaquine single dose 3 days for ASAQ and 1 day for Primaquine Screening of all household members and immediate 10-15 neighboring households of a passively detected index case, whether symptomatic or not, followed by treatment with ASAQ+LDPQ in case of positive RDT results. Women in the first trimester of pregnancy will be treated with quinine, while those in second and third trimesters will receive ACT, but neither will get single dose primaquine 65000
Experimental Group Focal Mass Drug Administration ASAQ once a day and primaquine single dose 3 days for ASAQ and 1 day for Primaquine Treating all household members and immediate 10-15 neighboring households of a passively detected index case, with ASAQ +LDPQ whether symptomatic or not and regardless of RDT result. Women in the first trimester of pregnancy will be treated with quinine tablets, while those in second and third trimesters will receive ACT, but neither will get single dosage primaquine 65000
Control Group Control ASAQ once a day and primaquine single dose 3 days for ASAQ and 1 day for Primaquine Passively detected malaria cases will receive ASAQ+LDPQ per national guidelines. All women and girls ages 12¿49 with an unknown pregnancy status, will require a negative pregnancy test before receiving LDPQ. 65000
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿ Arm 1(Reactive case detection): all household members and immediate 10-15 neighboring households of a passively detected index case, whether symptomatic or not, with positive RDT results. ¿ Arm 2 (focal Mass drug administration) : all household members and immediate 10-15 neighboring households of a passively detected index case, whether symptomatic or not and regardless of RDT result. ¿ Arm 3 (Control): Passively detected malaria cases. Patients living in a cluster with a planned focal IRS campaign in the following 2 years 0 Year(s) 100 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 06/04/2016 Comité d'éthique de la recherche biomédicale
Ethics Committee Address
Street address City Postal code Country
8, rue Karikja, B.P. 8145 Tsaralalana Antananarivo 101 Madagascar
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Malaria Annual Parasite Incidence (API) in Reactive Case Detection (RCD) and focal Mass drug administration fMDA arms compared to a control arm. 2 years
Secondary Outcome PCR prevalence of malaria Year 0 (baseline), Year 1 and Year 2 of each intervention group of study clusters
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Miarinarivo district Miarinarivo district Madagascar
Ambohimahasoa district Ambohimahasoa district Madagascar
Andramasina district Andramasina district Madagascar
Lalangina district Lalangina district Madagascar
Soavinandriana district Soavinandriana district Madagascar
Antanifotsy district Antanifotsy district Madagascar
Antsirabe II Antsirabe II Madagascar
Arivonimamo district Arivonimamo district Madagascar
Fandriana district Fandriana district Madagascar
Isandra district Isandra district Madagascar
Ambatolampy district Ambatolampy district Madagascar
Ambositra district Ambositra district Madagascar
Vohibato district Vohibato district Madagascar
Ambohidratrimo district Ambohidratrimo district Madagascar
FUNDING SOURCES
Name of source Street address City Postal code Country
President's Malaria Initiative (PMI) B.P. 5253, Lot 207 A, Point Liberty, Andranoro - Antehiroka Antananarivo 105 Madagascar
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Institut Pasteur de Madagascar B.P. 1274 Ambatofotsikely Avaradoha Antananarivo 101 Madagascar Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Centers for Disease Control and Prevention (CDC) 1600 Clifton Road Atlanta 30329 United States of America
National Malaria Control Program (NMCP) Androhibe Antananarivo 101 Madagascar
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Milijaona Randrianarivelojosia milijaon@pasteur.mg +261 20 22 412 72 B.P. 1274, Ambatofotsikely Avaradoha
City Postal code Country Position/Affiliation
Antananarivo 101 Madagascar Head of Malaria Unit/ Institut Pasteur de Madagascar
Role Name Email Phone Street address
Principal Investigator Laura Steinhardt iyp6@cdc.gov 404-718-4794 1600 Clifton Road
City Postal code Country Position/Affiliation
Atlanta 30329 United States of America CDC
Role Name Email Phone Street address
Public Enquiries Judicaelle Irinantenaina judi@pasteur.mg +261 20 22 412 72 B.P. 1274, Ambatofotsikely Avaradoha
City Postal code Country Position/Affiliation
Antananarivo 101 Madagascar Clinical Research Coordinator/ Institut Pasteur Madagascar
Role Name Email Phone Street address
Scientific Enquiries Milijaona Randrianarivelojosia milijaon@pasteur.mg +261 20 22 412 72 B.P. 1274, Ambatofotsikely Avaradoha
City Postal code Country Position/Affiliation
Antananarivo 101 Madagascar Head of Malaria Unit/ Institut Pasteur de Madagascar
REPORTING
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