A Trial of Antimalarial Drugs Used in Pregnancy in Tanzania

• Status: Completed
• Trial end date: 2007-09-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gates Malaria Partnership; London School of Hygiene and Tropical Medicine
• Collaborator: National Institute for Medical Research, Tanzania
• Treatments: Amodiaquine; Artesunate; Chlorproguanil; Dapsone; Proguanil

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