A Trial of Antimalarial Drugs Used in Pregnancy in Tanzania

NCT00146731 | Completed Phase 3 DMC

• 1 other identifier: ITCRVG04
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria

Keywords

malaria; pregnancy; treatment; Africa; Tanzania

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (11)

• 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

Interventions

SP DRUG

SP + amodiaquine DRUG

AQ + artesunate DRUG

chlorproguanil-dapsone DRUG

Eligibility Criteria

• Age: 15 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Is 14-34 weeks pregnant on the day of attending the ANC clinic or OPD;
• Has a viable foetus, defined by presence of foetal heartbeat by sonicaid or pinnard (foetal heartbeat is not heard until 14 weeks);
• Is able to take study drugs by the oral route;
• Is able to attend stipulated days for follow up clinic and provide specimens;
• 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).

You may not qualify if:

• Severe and complicated forms of malaria (as defined by WHO, 1996);
• Pregnancy in the first trimester;
• A mixed plasmodial infection;
• Complicated pregnancy, e.g. signs/symptoms of toxaemia of pregnancy;
• or more abortions or stillbirths;
• Presence of concomitant disease masking assessment of the response to treatment ;
• An intake of drugs contraindicated in pregnancy, e.g. tetracycline, cotrimoxazole or a macrolide antibiotic;
• An intake of drugs with effective antimalarial activity within the last 2 weeks.
• 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);
• 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.
• Multiple gestation pregnancies, eg twins
• Mother aged 38 years or above

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• National Institute for Medical Research, Tanzania: collaborator

Study Sites (1)

Muheza Designated District Hospital

Muheza, Tanga, PB, Tanzania

Location

Related Publications (1)

• Mutabingwa TK, Muze K, Ord R, Briceno M, Greenwood BM, Drakeley C, Whitty CJ. Randomized trial of artesunate+amodiaquine, sulfadoxine-pyrimethamine+amodiaquine, chlorproguanal-dapsone and SP for malaria in pregnancy in Tanzania. PLoS One. 2009;4(4):e5138. doi: 10.1371/journal.pone.0005138. Epub 2009 Apr 8.

  PMID: 19352498 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Amodiaquine; Artesunate; chloroguanil, dapsone drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons

Study Officials

• Theonest K Mutabingwa, MD PhD

  LSHTM/NIMR

  STUDY DIRECTOR

• Christopher JM Whitty, FRCP

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

• Daniel Chandramohan, MD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 5, 2005
• First Posted: September 7, 2005
• Study Start: January 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: January 12, 2017

Record last verified: 2017-01

Locations

TA (1)