Comparison of ISTp- PYRAMAX-US-RDT to IPTp-SP to Prevent Malaria in Pregnant Women in DRC (ULTRAPYRAPREG)

NCT ID: NCT04783051

Last Updated: 2022-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-06
• Study Completion Date: 2022-06-22

Brief Summary

In endemic settings Plasmodium falciparum (Pf) can sequester in the placenta resulting in low peripheral parasitemia and false negative malaria diagnosis in pregnant women. Intermittent Preventive Treatment in pregnant women with Sulphadoxine-Pyrimethamine (IPTp-SP) is one of the World Health Organization's recommended malaria control strategies in sub-Saharan African countries. The strategy overcomes the risk of misdiagnosis of malaria in pregnant women by treating them all with SP according to predetermined schedules, but the strategy is now threatened by the spread of Plasmodium parasite resistant strains. As a necessary alternative, Intermittent Screening and Treatment in pregnancy (ISTp), aims on the monthly screening of pregnant women with a malaria rapid diagnostic test (RDT) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. The ISTp depends on the performance of the diagnostic tests, and the use of ultrasensitive RDTs (us-RDTs), which have a higher analytical sensitivity than conventional RDTs, should improve the efficacy of the strategy.

Unlike IPTp-SP, ISTp prevents overuse of antimalarials and thus limits drug pressure on malaria parasites. This advantage could be potentiated by using, for pregnant women, an ACT that is not yet used or should not be used in the field for other strata of the population. The recently approved new ACT combination, Pyronaridine - Artesunate (Pyramax®) is the ideal candidate for this purpose.

This study will compare the effects of the ISTp using an us-RDT and Pyramax® (ISTp-US-Py) with the standard IPTp-SP on maternal malaria indicators (malaria infection, parasite density), maternal anemia, spontaneous abortions or intrauterine deaths during pregnancy, fetal morbidity (preterm birth, low birth weight, small for gestational age) and neonatal mortality at delivery in both study groups through conducting a randomized clinical trial enrolling second trimester pregnant women in Maternité Esengo Health Center, located in Kisenso, Kinshasa, the Democratic Republic of the Congo (DRC), a malaria perennial transmission area.

The results generated from this study will be essential for the National Malaria Control Program in the selection and implementation of new malaria control policies and addresses the effectiveness of IPTp-SP decline among pregnant women in the DRC.

Detailed Description

1. Introduction Malaria is a threat for pregnant women and their offspring in endemic settings (1, 2). Plasmodium falciparum (Pf) can sequester in the placenta during pregnancy, resulting in low peripheral parasitemia. As a consequence, malaria diagnostic tests are often false negative in pregnant women who actually do have a Pf malaria infection (3, 4).

Intermittent Preventive Treatment in pregnant women with Sulfadoxine-Pyrimethamine (IPTp-SP) is one of the World Health Organization (WHO)'s recommended malaria control strategies in sub-Saharan African countries (2). The IPTp-SP strategy surmounts the potential misdiagnosis of malaria in pregnant women by treating them all with SP at pre-determined schedules during the antenatal care (ANC) visits. The efficacy of IPTp-SP is dose dependent and relies on ANC coverage. However, the spread of Plasmodium SP resistant strains now threatens the efficacy of the IPTp-SP and can lead to the proliferation of placental resistant parasites in pregnant women (5-9).

As an alternative for IPTp-SP, Intermittent Screening and Treatment in pregnancy (ISTp) may be considered as an option (10). ISTp comprises of monthly screening of pregnant women with a malaria RDT and treatment of positive cases with an artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. The ISTp depends on the performance of the diagnostic tests and the use of ultrasensitive RDTs (us-RDTs), which have a higher sensitivity than conventional RDTs (11, 12), can avoid false negative that would prevent the method from being effective.

Unlike IPTp-SP, ISTp prevents overuse of antimalarials and, thus, limits drug pressure on malaria parasites (10). This advantage could be potentiated by using an ACT that is not yet used or should not be used by the national malaria control for other strata of the population than pregnant women. Pyronaridine - Artesunate (Pyramax®), a newly approved antimalarial is the ideal candidate for this purpose in Democratic Republic of Congo (DRC). Pyramax®, approved for use in malaria endemic countries since 2015, is used in the field to treat malaria in children and adults (13). There is little information on the safety of Pyramax® during pregnancy, however, Pyronaridine unintentionally administered successfully treated at least 40 cases of malaria in late pregnancy (14) and, a review reported that ACTs, although Pyramax® was not included in, are generally very effective and well tolerated during the second and third trimesters (15).

The hypothesis of this study is that the ISTp using Pyramax® for the treatment and performed with the us-RDT (ISTp-US-Py) is non inferior than IPTp-SP for the prevention of maternal malaria (malaria infection, parasite density), maternal anemia, spontaneous abortions or intrauterine death during pregnancy, fetal morbidity (premature birth, low birth weight, small for gestational age) and neonatal mortality at childbirth.

Conditions

Malaria in Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

IPTp-SP

The IPTp-SP group will be pregnant women who will receive the standard regimen recommended by the Malaria National Control Program (MNCP) at week 16, 28, 32 and 36 of their pregnancy

Group Type: ACTIVE_COMPARATOR

Sulfadoxine pyrimethamine

Intervention Type: DRUG

Intermittent Preventive Treatment in pregnant women with Sulfadoxine-Pyrimethamine

ISTp-US-Py

The ISTp-US-Py group will comprise pregnant women who will be screened monthly from the beginning of the 2nd trimester with ultra-sensitive -RDT and who will be treated with Pyramax® if the test is positive

Group Type: EXPERIMENTAL

Pyramax

Intervention Type: DRUG

Intermittent screening using ultra-sensitive malaria Rapid Diagnostic test and treatment using Pyronaridine - Artesunate (PYRAMAX®)

Interventions

Sulfadoxine pyrimethamine

Intermittent Preventive Treatment in pregnant women with Sulfadoxine-Pyrimethamine

Intervention Type: DRUG

Pyramax

Intermittent screening using ultra-sensitive malaria Rapid Diagnostic test and treatment using Pyronaridine - Artesunate (PYRAMAX®)

Intervention Type: DRUG

Other Intervention Names

IPTp-SP; ISTp-US-Py

Eligibility Criteria

Inclusion Criteria

1. Gestation ≥16 weeks;

2. Age: ≥18 years;

3. Residence within the health facility catchment area;

4. Willing to adhere to study requirements and to deliver at the health facility.

5. Willing to provide written informed consent; if the woman is illiterate, she can choose an impartial witness, not related to the study, to accompany her during the informant consent process and they will both sign the informed consent form

Exclusion Criteria

1. Known history of allergy to SP or to an ACT

2. An ongoing antibioprophylaxis with cotrimoxazole,

3. Current issue requiring hospital admission (including severe malaria as defined by WHO)

4. Pregnancy at high risk

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

University of Kinshasa

OTHER

Sponsor Role: lead

Responsible Party

Vivi Maketa

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Maternité Esengo

Kinshasa, , Democratic Republic of the Congo

Countries

Democratic Republic of the Congo

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Related Links

https://www.pyrapreg.org/about-project/

The PYRAPREG project

https://www.era-learn.eu/network-information/networks/edctp-ii/clinical-trials-and-operational-research-studies-to-optimise-the-use-of-products-for-poverty-related-diseases-in-mothers-newborns-children-and-or-adolescents/efficacy-and-safety-of-a-newly-registered-artemisinin-based-combination-pyronaridine-artesunate-pyramax-r-for-the-treatment-of-uncomplicated-malaria-in-african-pregnant-women

Clinical trials and operational research studies to optimise the use of products for poverty-related diseases in mothers, newborns, children and/or adolescents

https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/18557slr015_fansidar_lbl.pdf

Pharmaceuticals R. FANSIDAR. brand of sulfadoxine and pyrimethamine TABLETS 1996

Other Identifiers

226/CNES/BN//PMMF/2020

Identifier Type: -

Identifier Source: org_study_id