Skip to main content
TTrialFinderData
TrialFinderData is for informational purposes only and does not provide medical advice. Always talk to your doctor.

Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

Safety of Antimalarials in the FIRst trimEster

A Multicentre Open-label, Non-inferiority Adaptive Platform Randomised Controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Antimalarials for the Treatment of Uncomplicated Malaria in the First Trimester of Pregnancy: Master Protocol

Safety of Antimalarials in the FIRst trimEster (NCT06962319) is a Phase 3 interventional studying Malaria, Pregnancy and Malaria, Antepartum, sponsored by Liverpool School of Tropical Medicine. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

The SAFIRE study aims to find effective treatments with acceptable safety for malaria in early pregnancy, a particularly sensitive time for the adverse consequences of malaria in pregnancy for both mother and baby. Currently, WHO recommends the antimalarial drug artemether-lumefantrine (AL) for the treatment of uncomplicated malaria in the first trimester of pregnancy. Other promising treatments are being rolled out in malaria-endemic countries for use in adults and children and data on current exposures in the first trimester are limited and insufficient to support a recommendation. This is due to the fact that pregnant women are often excluded from clinical trials to protect fetuses, unintentionally depriving them of newer, potentially better treatments. Instead, they often received older, less effective drugs. The International Council for Harmonisation (ICH E21) and stringent regulatory authorities (e.g. EMA, FDA and MHRA) now encourage pregnant women to be included in well-designed studies to ensure they can safely benefit from medical advances. This study will compare AL with the newer antimalarial drugs that have shown no significant safety concerns in laboratory studies, accidental use during early pregnancy, or trials in later pregnancy stages. The main goal is to see if these new drugs work as well as AL in treating malaria and are safe for the mother, her pregnancy and the developing baby. The newer antimalarials being tested also offer additional benefits to pregnant women, such as preventing new malaria infections for longer after treatment than the current standard treatment (AL). Also, they can be taken just once a day instead of twice daily, like AL. A simpler dosing schedule could improve adherence to the study medication, meaning women are more likely to take the full course of treatment as prescribed. This, in turn, enhances its effectiveness in real-world settings. Future antimalarials to be tested will include those with improved resistance profiles, offering more effective options for combating drug-resistant strains. SAFIRE uses a special "Bayesian Adaptive Platform Trial" (APT) design. This open-ended approach allows researchers to add new interventions under the same protocol, leveraging the existing trial network with infrastructure. The use of a common protocol with innovative adaptive statistical design allows the trial to stop early if it becomes clear that the new drugs are unsafe. This multi-centre trial will be conducted in several countries in Africa where malaria is very common. Women will be randomly assigned to receive either AL or one of the new treatments. Participants will be seen daily for 4 days, then weekly for 6 weeks to assess the response to treatment, and then monthly until delivery. Their health and outcomes will be closely monitored during and after pregnancy. Newborns will be followed for 6 months. An independent data safety and monitoring board (DSMB) will regularly monitor safety data as it accumulates. By finding more treatment options, this study could improve care for pregnant women with malaria and lead to better health for mothers and babies in areas where malaria is widespread. The results will help inform global health policies and potentially change how we treat malaria in early pregnancy.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Malaria, Pregnancy, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 1,510 participants makes this one of the larger Malaria, Pregnancy trials currently registered. Trials at this scale are typically global, run across many sites, and designed to generate the definitive evidence package for an FDA approval submission or a label expansion.

Who May Be Eligible (Plain English)

Who May Qualify: - ≥2 weeks and \<14 weeks (13-6/7 weeks inclusive) gestation from the last menstrual period (LMP) as assessed by echography - Microscopy confirmed P. falciparum mono or mixed infections, regardless of symptoms. - Emancipated minor and aged ≥16 years - Haemoglobin ≥ 7 g/dL - Residence within the health facility catchment area - Willingness to adhere to study requirements and to deliver the baby at the local health facility - Willingness to adhere to study requirements and to deliver the baby at the local health facility Who Should NOT Join This Trial: - Known allergy to any of the study drugs - History of known pregnancy complications or poor obstetric history, such as repeated miscarriages, stillbirths, or eclampsia - History or presence of major illnesses likely to influence pregnancy outcome - Known HIV positive - Any significant illness at the time of screening requiring hospitalisation, including severe malaria - Intent to move out of the study catchment area before delivery or planned delivery out of the catchment area - Recent (2 weeks) treatment with antimalarials or antimicrobials with antimalarial activity (chloroquine, AL, DP, PA, SPAQ, ASAQ, MQAS, azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP) - Twin/multiple pregnancy detected - Non-viable pregnancy confirmed by ultrasound or doppler - Known history or evidence of clinically significant cardiovascular disorders or family history of sudden death or congenital long QT syndrome or current co administration of other drugs that might contribute to a prolonged QTc interval or cause "Torsades de Point" - Chronic medical condition requiring frequent medications (e.g., TB, suspected hepatic lesions, liver disease, sickle cell disease, diabetes, epilepsy, asthma and hypertension) - Prior randomisation in this study during the current pregnancy Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * ≥2 weeks and \<14 weeks (13-6/7 weeks inclusive) gestation from the last menstrual period (LMP) as assessed by echography * Microscopy confirmed P. falciparum mono or mixed infections, regardless of symptoms. * Emancipated minor and aged ≥16 years * Haemoglobin ≥ 7 g/dL * Residence within the health facility catchment area * Willingness to adhere to study requirements and to deliver the baby at the local health facility * Willingness to adhere to study requirements and to deliver the baby at the local health facility Exclusion Criteria: * Known allergy to any of the study drugs * History of known pregnancy complications or poor obstetric history, such as repeated miscarriages, stillbirths, or eclampsia * History or presence of major illnesses likely to influence pregnancy outcome * Known HIV positive * Any significant illness at the time of screening requiring hospitalisation, including severe malaria * Intent to move out of the study catchment area before delivery or planned delivery out of the catchment area * Recent (2 weeks) treatment with antimalarials or antimicrobials with antimalarial activity (chloroquine, AL, DP, PA, SPAQ, ASAQ, MQAS, azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP) * Twin/multiple pregnancy detected * Non-viable pregnancy confirmed by ultrasound or doppler * Known history or evidence of clinically significant cardiovascular disorders or family history of sudden death or congenital long QT syndrome or current co administration of other drugs that might contribute to a prolonged QTc interval or cause "Torsades de Point" * Chronic medical condition requiring frequent medications (e.g., TB, suspected hepatic lesions, liver disease, sickle cell disease, diabetes, epilepsy, asthma and hypertension) * Prior randomisation in this study during the current pregnancy

Treatments Being Tested

DRUG

dihydroartemisinin-piperaquine (DP)

Weight-based dosing of 3 (\<60kg), 4 (6-80kg) or 5 (\>80 kg) 40/320 mg tablets of dihydroartemisinin-piperaquine given once daily for 3 days

DRUG

Pyronaridine-artesunate (PA)

Weight-based dosing of 2 (24-\<45 kg), 3 (45-\<65kg), or 4 (\>=65 kg) 180/60 mg tablets of pyronaridine-artesunate, once daily for 3 days.

DRUG

Artemether-lumefantrine

1 x 80/480 or 4 x 20/120 mg tablets of artemether-lumefantrine, given twice daily, approximately 8 hours apart for 3 days

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Clinical Research Unit of Nanoro (CRUN), Institut de Recherche en Sciences de la Santé, Direction Régionale de l'Ouest (IRSS-DRO)
Nanoro, Burkina Faso
KEMRI Centre for Global Health Research (CGHR)
Kisumu, Kenya
Malaria Research and Training Center, University of Sciences, Techniques, and Technologies of Bamako (USTTB),
Bamako, Mali

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06962319), the sponsor (Liverpool School of Tropical Medicine), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06962319 clinical trial studying?

The SAFIRE study aims to find effective treatments with acceptable safety for malaria in early pregnancy, a particularly sensitive time for the adverse consequences of malaria in pregnancy for both mother and baby. Currently, WHO recommends the antimalarial drug artemether-lumefantrine (AL) for the treatment of uncomplicated malaria in the first trimester of pregnancy. Other promising treatments are being rolled out in malaria-endemic countries for use in adults and children and data on current exposures in the first trimester are limited and insufficient to support a recommendation. This is d… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06962319?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06962319?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06962319. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06962319. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.