Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy

This study has been completed.
Sponsor:
Collaborators:
Medecins Sans Frontieres
University of Cape Town
Sholklo Malaria Research Unit
Information provided by:
Epicentre
ClinicalTrials.gov Identifier:
NCT00495508
First received: July 2, 2007
Last updated: May 12, 2010
Last verified: May 2010
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Quinine
Drug: artemether / lumefantrine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Epicentre:

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

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

Estimated Enrollment: 300
Study Start Date: October 2006
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
  Hide Detailed Description

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
  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00495508

Locations
Uganda
Epicentre
Mbarara, Mbarara District, Uganda
Sponsors and Collaborators
Epicentre
Medecins Sans Frontieres
University of Cape Town
Sholklo 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
  More Information

No publications provided by Epicentre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr Patrice Piola, Epicentre
ClinicalTrials.gov Identifier: NCT00495508     History of Changes
Other Study ID Numbers: Mba/06/MIP
Study First Received: July 2, 2007
Last Updated: May 12, 2010
Health Authority: France: Institutional Ethical Committee

Keywords provided by Epicentre:
Quinine
Artemether
Lumefantrine
malaria
Uganda
Artemisinin- based combination therapy
pregnancy
Malaria In Pregnancy

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Lumefantrine
Artemether
Artemisinins
Quinine
Artemether-lumefantrine combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Coccidiostats
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on October 02, 2014