Additional Screening With Sensitives RDTs and Malaria

NCT04147546 | Completed Phase 3 DMC

• 1 other identifier: NCT04147546
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

Brief Summary

National malaria control strategies in pregnant women relies primarily on effective case management along with the use of long lasting insecticide-treated nets (LLINs)throughout pregnancy and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) in the second and third trimesters in malaria-endemic regions in sub-Saharan Africa (SSA). For the latter, 3 or more doses are recommended by the national malaria control program (NMCP) but available data suggests that only 19% of eligible women received this in 2016 despite observed high attendance to antenatal clinic (ANC). Adherence to IPTp may be affected by perceptions, acceptability and contextual factors that need to be understood and therefore improve the effectiveness of this health interventions. In addition, all malaria cases should be confirmed either by microscopy or using a rapid diagnostic test (RDTs) before any treatment. Despite the crucial role of RDTs in improving malaria case management SSA, many malaria cases are missed in pregnant women due to the power performance of recommended RDTs which are unable to detect very low parasitaemia. Identifying lower density infections in pregnant women by the use of highly-sensitive RDTs and clearing them with an effective ACT could improve the outcome of the pregnancy in addition to IPTp-SP.

Conditions

Plasmodium Falciparum Malaria; Malaria Diagnosis

Outcome Measures

Primary Outcomes (3)

• Placental malaria prevalence

  The prevalence of placental malaria infection will be determined in the two arms. Placentas will be identified as not infected (no evidence of parasite or pigment); active infection (presence of parasites and pigment) and chronic infection (absence of parasites and presence of pigment)

  36 months

• Low birthweight prevalence

  The prevalence of low birthweight (defined as birth weight less than 2,500 g) will be compared between the two arms.

  36 months

• Peripheral maternal malaria infection prevalence

  At delivery, malaria will be diagnosed using peripheral thick smears. Parasite density will be estimated by counting the number of asexual parasites per 200 leukocytes in the thick blood film and assuming white blood cells (WBC) count of 8,000/μl

  36 months

Study Arms (2)

Intervention arm

EXPERIMENTAL

A full course of dihydroartemisinin-piperaquine (DP) over 3 days. The first dose of DP will be administered under direct observation at the antenatal care clinic (ANC) and the subsequent doses of the intervention in days 2 and 3 will be taken unsupervised at home. At each ANC visit, study nurses will perform an HS-RDT for participants in this arm. Reminders will be sent in this group in order to improve IPTp-SP uptake

Diagnostic Test: Additional screening using ultra sensitive RDTs; Drug: Dihydroartemisinin-piperaquin; Other: Reminders

Control arm

NO INTERVENTION

A full course of artemether-lumefantrine (AL) over 3 days. The first dose of AL will be administered under direct observation at the antenatal care clinic (ANC) and the subsequent doses of the intervention in days 2 and 3 will be taken unsupervised at home. At each ANC visit, study nurses will perform a conventional RDT for participants in this arm if the participant have symptoms suggestive of malaria. No reminder will be sent

Interventions

Additional screening using ultra sensitive RDTs DIAGNOSTIC_TEST

At each ANC visit, study nurses will perform an HS-RDT for participants in the intervention arm

Also known as: Malaria Ag Pf ultra-sensitive RDT

Intervention arm

Dihydroartemisinin-piperaquin DRUG

All pregnant women with a positive HS-RDT will be treated with a full course of dihydroartemisinin-piperaquine (DP) over 3 days. The first dose of DP will be administered under direct observation at the antenatal care clinic (ANC) and the subsequent doses of the intervention in days 2 and 3 will be taken unsupervised at home

Intervention arm

Reminders OTHER

Before each scheduled ANC visit, reminders using SMS or phone call will be used. This is order to increase ANC attendance

Intervention arm

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Gestational age of 16 to 24 weeks at their first booking
• At least (≥) 16 years old
• Residence in the study area and intention to stay in the area for the duration of the pregnancy and for delivery
• Willing to deliver at the health facility
• Willing to provide biological samples as and when required during the study period (blood and placental biopsy)
• Ability to provide written informed consent

You may not qualify if:

• A history of sensitivity to sulphonamides or to any of the study drugs;
• History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;
• History or presence of major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;
• Any significant illness at the time of screening that requires hospitalization, including severe malaria;
• Intent to move out of the study catchment area before delivery or deliver at relative's home out of the catchment area.
• Prior enrolment in the study or concurrent enrolment in another study.

Sponsors & Collaborators

• Institut de Recherche en Sciences de la Sante, Burkina Faso: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Institut de Recherche en Sciences de la Santé/ Clinical Research Unit of Nanoro

Ouagadougou, Kadiogo, 218 CMS 11, Burkina Faso

Location

Related Publications (12)

• Dellicour S, Tatem AJ, Guerra CA, Snow RW, ter Kuile FO. Quantifying the number of pregnancies at risk of malaria in 2007: a demographic study. PLoS Med. 2010 Jan 26;7(1):e1000221. doi: 10.1371/journal.pmed.1000221.

  PMID: 20126256 BACKGROUND

• Desai M, ter Kuile FO, Nosten F, McGready R, Asamoa K, Brabin B, Newman RD. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis. 2007 Feb;7(2):93-104. doi: 10.1016/S1473-3099(07)70021-X.

  PMID: 17251080 BACKGROUND

• COSMIC Consortium. Community-based Malaria Screening and Treatment for Pregnant Women Receiving Standard Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine: A Multicenter (The Gambia, Burkina Faso, and Benin) Cluster-randomized Controlled Trial. Clin Infect Dis. 2019 Feb 1;68(4):586-596. doi: 10.1093/cid/ciy522.

  PMID: 29961848 BACKGROUND

• Radeva-Petrova D, Kayentao K, ter Kuile FO, Sinclair D, Garner P. Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment. Cochrane Database Syst Rev. 2014 Oct 10;2014(10):CD000169. doi: 10.1002/14651858.CD000169.pub3.

  PMID: 25300703 BACKGROUND

• van Eijk AM, Hill J, Larsen DA, Webster J, Steketee RW, Eisele TP, ter Kuile FO. Coverage of intermittent preventive treatment and insecticide-treated nets for the control of malaria during pregnancy in sub-Saharan Africa: a synthesis and meta-analysis of national survey data, 2009-11. Lancet Infect Dis. 2013 Dec;13(12):1029-42. doi: 10.1016/S1473-3099(13)70199-3. Epub 2013 Sep 18.

  PMID: 24054085 BACKGROUND

• Gutman J, Kalilani L, Taylor S, Zhou Z, Wiegand RE, Thwai KL, Mwandama D, Khairallah C, Madanitsa M, Chaluluka E, Dzinjalamala F, Ali D, Mathanga DP, Skarbinski J, Shi YP, Meshnick S, ter Kuile FO. The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women. J Infect Dis. 2015 Jun 15;211(12):1997-2005. doi: 10.1093/infdis/jiu836. Epub 2015 Jan 6.

  PMID: 25564249 BACKGROUND

• Ruizendaal E, Tahita MC, Geskus RB, Versteeg I, Scott S, d'Alessandro U, Lompo P, Derra K, Traore-Coulibaly M, de Jong MD, Schallig HDFH, Tinto H, Mens PF. Increase in the prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso. Malar J. 2017 Apr 28;16(1):179. doi: 10.1186/s12936-017-1831-y.

  PMID: 28454537 BACKGROUND

• Kakuru A, Jagannathan P, Muhindo MK, Natureeba P, Awori P, Nakalembe M, Opira B, Olwoch P, Ategeka J, Nayebare P, Clark TD, Feeney ME, Charlebois ED, Rizzuto G, Muehlenbachs A, Havlir DV, Kamya MR, Dorsey G. Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy. N Engl J Med. 2016 Mar 10;374(10):928-39. doi: 10.1056/NEJMoa1509150.

  PMID: 26962728 BACKGROUND

• Hofmann NE, Gruenberg M, Nate E, Ura A, Rodriguez-Rodriguez D, Salib M, Mueller I, Smith TA, Laman M, Robinson LJ, Felger I. Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination: an in-depth molecular community cross-sectional study. Lancet Infect Dis. 2018 Oct;18(10):1108-1116. doi: 10.1016/S1473-3099(18)30411-0. Epub 2018 Aug 28.

  PMID: 30170986 BACKGROUND

• Das S, Jang IK, Barney B, Peck R, Rek JC, Arinaitwe E, Adrama H, Murphy M, Imwong M, Ling CL, Proux S, Haohankhunnatham W, Rist M, Seilie AM, Hanron A, Daza G, Chang M, Nakamura T, Kalnoky M, Labarre P, Murphy SC, McCarthy JS, Nosten F, Greenhouse B, Allauzen S, Domingo GJ. Performance of a High-Sensitivity Rapid Diagnostic Test for Plasmodium falciparum Malaria in Asymptomatic Individuals from Uganda and Myanmar and Naive Human Challenge Infections. Am J Trop Med Hyg. 2017 Nov;97(5):1540-1550. doi: 10.4269/ajtmh.17-0245. Epub 2017 Aug 18.

  PMID: 28820709 BACKGROUND

• Vasquez AM, Medina AC, Tobon-Castano A, Posada M, Velez GJ, Campillo A, Gonzalez IJ, Ding X. Performance of a highly sensitive rapid diagnostic test (HS-RDT) for detecting malaria in peripheral and placental blood samples from pregnant women in Colombia. PLoS One. 2018 Aug 2;13(8):e0201769. doi: 10.1371/journal.pone.0201769. eCollection 2018.

  PMID: 30071004 BACKGROUND

• Tahita MC, Sondo P, Kabore B, Ilboudo H, Rouamba T, Sanou H, Ouedraogo K, Compaore A, Lompo P, Ouedraogo F, Sawadogo S, Derra K, Sawadogo YE, Some AM, Nana M, Sorgho H, Traore-Coulibaly M, Bassat Q, Tinto H. Impact and operational feasibility of adding malaria infection screening using an ultrasensitive RDT for placental and fetal outcomes in an area of high IPTP-SP coverage in Burkina Faso: the ASSER MALARIA pilot study protocol. Pilot Feasibility Stud. 2022 Oct 1;8(1):221. doi: 10.1186/s40814-022-01181-2.

  PMID: 36183100 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: November 1, 2019
• Study Start: August 31, 2020
• Primary Completion: August 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 30, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: At the end of the study and after all publications accepted

Locations

BU (1)