A Trial of Antimalarial Drugs Used in Pregnancy in Tanzania

This study has been completed.
Sponsor:
Collaborator:
National Institute for Medical Research, Tanzania
Information provided by:
Gates Malaria Partnership
ClinicalTrials.gov Identifier:
NCT00146731
First received: September 5, 2005
Last updated: February 17, 2010
Last verified: February 2010
  Purpose

Pregnant women are vulnerable to malaria, with significant implications both for their health and for the pregnancy. Sulfadoxine-pyrimethamine (SP) is currently the first line drug for the treatment of malaria in pregnancy in Tanzania and surrounding countries, but resistance is emerging rapidly. Alternative drugs must be found, and new drugs and drug combinations are being recommended by many for deployment as first line treatment at the point that SP resistance forces a policy change. However, there are few data on the safety and efficacy of these combinations in pregnant women. This randomised trial aims to assess efficacy and safety, including birth outcome, in pregnant women with malaria in the second or third trimesters. A total of 900 pregnant women will be randomised either to standard treatment (SP) or to one of three potential drugs, or drug combinations recently recommended by a WHO expert panel. These will be SP-amodiaquine, chlorproguanil-dapsone (Lapdap), and amodiaquine-artesunate. Primary outcome will be treatment failure. Secondary outcomes will include 28 day slide clearance, maternal side effects, foetal viability and birth outcome.


Condition Intervention Phase
Malaria
Drug: SP
Drug: SP + amodiaquine
Drug: AQ + artesunate
Drug: chlorproguanil-dapsone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treating Malaria During Pregnancy: A Randomized Trial of Potential Options for Treatment in an Area of High Drug Resistance in Tanzania

Resource links provided by NLM:


Further study details as provided by Gates Malaria Partnership:

Primary Outcome Measures:
  • The primary end-point of the trial will be treatment failure. This is defined above.

Secondary Outcome Measures:
  • Incidence of foetal death during treatment, defined as absence of foetal heartbeat assessed by Doppler
  • Hypoglycaemia requiring treatment
  • Parasite recrudescence or re-infection on day 28
  • Parasite clearance on day 3
  • Level of recovery of haemoglobin on day 14
  • Fever clearance time
  • Incidence of perinatal and neonatal mortality, assessed 4-6 weeks after due date of delivery
  • Clinically apparent neonatal abnormality, assessed 4-6 weeks after due date of delivery
  • Placental malaria
  • Preterm delivery
  • Other adverse events during treatment

Enrollment: 310
Study Start Date: January 2004
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years to 38 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A pregnant woman who has either a positive blood smear for P.falciparum with at least 1000 asexual parasites/uL in an asymptomatic woman

or any of the following symptoms within 2 days prior to consultation:

  • history of fever;
  • headache,
  • vomiting,
  • chills/rigors,
  • and/or any of the following signs: temperature >37.50C and <39.50C, Hb>5 and <9 g/dl together with P.falciparum parasitaemia at any density

and (in both cases) the following:

  1. Has no exclusion criterion (see below);
  2. Is 14-34 weeks pregnant on the day of attending the ANC clinic or OPD;
  3. Has a viable foetus, defined by presence of foetal heartbeat by sonicaid or pinnard (foetal heartbeat is not heard until 14 weeks);
  4. Is able to take study drugs by the oral route;
  5. Is able to attend stipulated days for follow up clinic and provide specimens;
  6. Gives informed written or witnessed verbal consent to participate by herself, and also through her parent/guardian if aged <15 years (in conformity to Tanzania Law).

Exclusion Criteria:

  1. Severe and complicated forms of malaria (as defined by WHO, 1996);
  2. Pregnancy in the first trimester;
  3. A mixed plasmodial infection;
  4. Complicated pregnancy, e.g. signs/symptoms of toxaemia of pregnancy;
  5. 23 or more abortions or stillbirths;
  6. Presence of concomitant disease masking assessment of the response to treatment ;
  7. An intake of drugs contraindicated in pregnancy, e.g. tetracycline, cotrimoxazole or a macrolide antibiotic;
  8. An intake of drugs with effective antimalarial activity within the last 2 weeks.
  9. Significantly abnormal baseline haematology (except anaemia) or clinical chemistry parameters, e.g. laboratory evidence of renal impairment (serum creatinine >2 mg/dl) or of hepatitis (alanine aminotransferase [ALT] >5 times upper limit of normal);
  10. Previous participation in the study: Women having a second episode of malaria after completing the 28-day follow up will have details recorded and offered quinine but not be re-enrolled.
  11. Multiple gestation pregnancies, eg twins
  12. Mother aged 38 years or above
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00146731

Locations
Tanzania
Muheza Designated District Hospital
Muheza, Tanga, Tanzania, PB
Sponsors and Collaborators
Gates Malaria Partnership
National Institute for Medical Research, Tanzania
Investigators
Study Director: Theonest K Mutabingwa, MD PhD LSHTM/NIMR
Principal Investigator: Christopher JM Whitty, FRCP LSHTM
Principal Investigator: Daniel Chandramohan, MD LSHTM
  More Information

No publications provided by Gates Malaria Partnership

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00146731     History of Changes
Other Study ID Numbers: ITCRVG04
Study First Received: September 5, 2005
Last Updated: February 17, 2010
Health Authority: Tanzania: Ministry of Health

Keywords provided by Gates Malaria Partnership:
malaria
pregnancy
treatment
Africa
Tanzania

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Amodiaquine
Antimalarials
Dapsone
Artesunate
Chlorproguanil
Proguanil
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Anti-Bacterial Agents
Amebicides
Antimetabolites

ClinicalTrials.gov processed this record on April 17, 2014