Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

May 31, 2022 updated by: Epicentre

A Randomised, Open-label Non-inferiority Trial of Artemether-lumefantrine Versus Quinine for the Treatment of Uncomplicated Falciparum Malaria During Pregnancy, Mbarara, Uganda (2006-2007)

A) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Title:

Efficacy and Safety of Quinine vs Artemether/Lumefantrine in uncomplicated malaria during pregnancy, Mbarara, Uganda (2006/2007).

Regulatory Status:

Investigational - Phase IV

Investigational Product and route:

  • Quinine hydrochloride, oral route.
  • Coartem® (Novartis Pharma AG, Basel, Switzerland), oral route.

Lead Investigator and Study Centre Primary objective - To establish that, in pregnant women with uncomplicated Plasmodium falciparum malaria, the PCR-adjusted efficacy of Artemether/Lumefantrine is not inferior to oral Quinine.

Secondary objectives

  • To define the pharmacokinetics of the combination artemether-lumefantrine (AL) in the treatment of uncomplicated P. falciparum infections in the last two trimesters of pregnancy.
  • To collect baseline data on maternal, obstetric and infant outcomes.
  • To estimate the incidence of malaria infection, both microscopic and sub-microscopic (by PCR) during pregnancy.
  • women attending Mbarara National Referral Hospital (MNRH) ante-natal clinic (ANC).
  • Women with a positive blood smear during follow-up will be invited to participate in a non-inferiority, open, randomised, non- inferiority trial comparing the efficacy and tolerance of Coartem® (Artemether-Lumefantrine) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion.
  • Women with uncomplicated malaria from the efficacy study, will be followed to obtain an efficacy endpoint at 42 days OR at delivery, whichever timepoint is the last.
  • Newborns will be followed monthly up to the age of 1 year.

Inclusion Criteria (Efficacy Study):

  • Pregnant woman
  • Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
  • Age of gestation: 13 weeks and beyond
  • Efficacy study signed informed consent form

Exclusion Criteria (Efficacy Study):

  • P. falciparum parasitaemia above 250,000 parasites/μl
  • Severe anaemia
  • Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
  • Known allergy to artemisinin derivatives, lumefantrine or quinine;
  • Previous participation in the efficacy study
  • Inability to attend the efficacy study follow-up schedule.

Study drugs and Administration

  • Group 1 (Active Control): Quinine hydrochloride (10 mg/Kg/8h for 7 days) administered orally.
  • Group 2 (Test): Coartem®, fixed Artemether-Lumefantrine (20/120 mg) GMP manufactured by Novartis Pharma AG (Basel, Switzerland), 4 tablets twice a day for 3 days with 200 ml of milk tea at each dose .

Endpoints

- Primary efficacy endpoint: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42.

  • Secondary efficacy endpoints:
  • PCR-corrected(ACPR)at delivery
  • Pharmacokinetic parameters
  • Symptom clearance Time
  • Proportion of patients who have fever cleared at Day 1, 2 and 3
  • Safety endpoints:
  • Incidence of any adverse events
  • Pregnancy outcome
  • Infant development during the first year of life

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
    • Mbarara District
      • Mbarara, Mbarara District, Uganda
        • Epicentre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

Cohort Study:

  • Weeks of pregnancy between 13 and 22 weeks
  • Resident in Mbarara Municipality (radius of 15km from MNRH)
  • Cohort study signed informed consent form

Efficacy Study:

  • Pregnant woman
  • Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)
  • Age of gestation: 13 weeks and beyond
  • Efficacy study signed informed consent form

Exclusion Criteria:

Efficacy Study:

  • P. falciparum parasitaemia above 250,000 parasites/μl
  • Severe anaemia
  • Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)
  • Known allergy to artemisinin derivatives, lumefantrine or quinine;
  • Previous participation in the efficacy study
  • Inability to attend the efficacy study follow-up schedule.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Quinine
Drug: Quinine
Active Comparator: Arthemeter lumefantrine
Drug: artemether / lumefantrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42 or at delivery.
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic parameters
Time Frame: 3.5 years
3.5 years
Incidence of adverse events
Time Frame: 3 years
3 years
Pregnancy outcome
Time Frame: 3.5 years
3.5 years
Infant development during the first year of life
Time Frame: 3 years
3 years
Histopathological findings in the placenta
Time Frame: 4 years
4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Epicentre

Collaborators

University of Cape Town
Medecins Sans Frontieres, Netherlands
Shoklo Malaria Research Unit

Investigators

  • Principal Investigator: Patrice Piola, MD, MPH, Epicentre
  • Study Chair: Philippe J Guerin, MD, MPH, PhD, Epicentre
  • Study Chair: Elizabeth Ashley, MB BS, Epicentre
  • Study Chair: Rose McGready, MD, PhD, Shoklo Malaria Research Unit (SMRU)
  • Study Chair: François Nosten, MD, PhD, SMRU

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2006

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

July 2, 2007

First Submitted That Met QC Criteria

July 2, 2007

First Posted (Estimate)

July 3, 2007

Study Record Updates

Last Update Posted (Actual)

June 3, 2022

Last Update Submitted That Met QC Criteria

May 31, 2022

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Mba/06/MIP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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