Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Malaria in Pregnancy

NCT01916954 | Completed Phase 3

• 1 other identifier: ALN5P
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria in pregnancy is a major cause of maternal and newborn morbidity and mortality in sub-Saharan Africa\]. Effective antimalarial preventive and treatment regimens can significantly reduce malaria-related morbidity and mortality in the mother and baby. However, therapeutic choices are limited by concerns about possible toxicity to the fetus and because of these concerns pregnant women are normally excluded from clinical trials. This, combined with the lack of adverse events reporting system, results in a scarcity of data on drug safety and efficacy in pregnancy. Moreover, changes in the maternal physiology in pregnancy often alter the pharmacokinetic of drugs. Artemether-lumefantrine (ALN) is a highly efficacious artemisinin-based combination therapy approved by the World Health Organisation for use in the 2nd and 3rd trimesters, although it is still infrequently used in pregnancy and there is uncertainty as to the optimum dose. The pharmacokinetics of ALN are altered in pregnancy, resulting in reduced plasma concentrations and while the standard adult dose is still effective in high transmission settings, where pregnant women have higher levels of immunity, efficacy is reduced significantly in low transmission settings where women have lower levels of immunity. Inadequate antimalarial treatment dosing in pregnancy risks treatment failure or breakthrough infection and exposure of malaria parasites to sub-therapeutic drug concentrations thus selecting for drug resistance.

Conditions

Malaria

Keywords

Malaria; Pregnancy; Plasmodium falciparum

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics measures

  Drug plasma concentration profiles for lumefantrine, artemether and dihydroartemisinin will be characterized for each patient. Ten samples per patient will be taken at fixed and random times.

  1 year

Secondary Outcomes (1)

• Tolerability and safety measures

  2 years

Other Outcomes (1)

• Efficacy measures

  1 year

Study Arms (2)

3-day artemether-lumefantrine

ACTIVE COMPARATOR

Standard artemether-lumefantrine regimen (3-day treatment)

Drug: 3-day artemether-lumefantrine

5-day artemether-lumefantrine

EXPERIMENTAL

Artemether-lumefantrine extended regimen (5-day treatment)

Drug: 5-day artemether-lumefantrine

Interventions

3-day artemether-lumefantrine DRUG

3-day artemether-lumefantrine

5-day artemether-lumefantrine DRUG

5-day artemether-lumefantrine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥18 and ≤ 45 years
• P. falciparum parasitemia ≥ 100 parasites/μL and less than 200.000 parasites/μL
• Hematocrit ≥21%
• Negative HIV test
• Negative pregnancy test\*
• Written informed consent provided
• Willing to stay for 3 or 5 days at the hospital and to comply with the follow-up schedule
• Gestational Age ≥ 14 weeks confirmed by ultrasound
• Singleton viable fetus

You may not qualify if:

• Severe malaria or signs of severe malaria
• Medical conditions requiring concomitant drug treatment or transfer to a different hospital
• Intake of artemether-lumefantrine within the two previous 2 weeks
• Known allergy to the study drugs
• Previous participation in this study or current participation in other studies
• Signs of labour
• Fetal abnormalities identified by ultrasound

Sponsors & Collaborators

• University of Oxford: lead
• University of Kinshasa: collaborator

Study Sites (1)

University of Kinshasa, Democratic Republic of Congo

Kinshasa, Republic of the Congo

Location

Related Publications (1)

• Onyamboko MA, Hoglund RM, Lee SJ, Kabedi C, Kayembe D, Badjanga BB, Turner GDH, Jackson NV, Tarning J, McGready R, Nosten F, White NJ, Day NPJ, Fanello C. A Randomized Controlled Trial of Three- versus Five-Day Artemether-Lumefantrine Regimens for Treatment of Uncomplicated Plasmodium falciparum Malaria in Pregnancy in Africa. Antimicrob Agents Chemother. 2020 Feb 21;64(3):e01140-19. doi: 10.1128/AAC.01140-19. Print 2020 Feb 21.

  PMID: 31818818 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Nicholas P Day, MD PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 1, 2013
• First Posted: August 6, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2014
• Last Updated: March 26, 2014

Record last verified: 2014-03

Locations

RE (1)