Treating Malaria During Pregnancy: A Randomized Trial of Potential Options for Treatment in an Area of High Drug Resistance in Tanzania
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 310
- 试验地点
- 2
- 主要终点
- The primary end-point of the trial will be treatment failure. This is defined above.
研究概览
简要总结
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.
详细描述
The objectives of this study are to assess the therapeutic efficacy and safety of SP as the current first line drug, and three other potential alternative combinations in treating uncomplicated falciparum malaria during pregnancy, in an area with appreciable levels of SP resistance and rising HIV seroprevalence. Specifically the study will compare the clinical and parasitological response to and the side effects of the following drug regimes:
- SP
- SP + amodiaquine (SPAQ)
- Chlorproguanil+dapsone (Lapdap)
- Amodiaquine + artesunate (AQAS)
TRIAL DESIGN
Primary end point
The primary end-point of the trial will be treatment failure. This will be defined as:-
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 38 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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:
- •Has no exclusion criterion (see below);
- •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).
排除标准
- •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;
- •23 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
结局指标
主要结局
The primary end-point of the trial will be treatment failure. This is defined above.
次要结局
- Parasite clearance on day 3
- Preterm delivery
- Fever clearance time
- Clinically apparent neonatal abnormality, assessed 4-6 weeks after due date of delivery
- Placental malaria
- Incidence of foetal death during treatment, defined as absence of foetal heartbeat assessed by Doppler
- Hypoglycaemia requiring treatment
- Level of recovery of haemoglobin on day 14
- Parasite recrudescence or re-infection on day 28
- Incidence of perinatal and neonatal mortality, assessed 4-6 weeks after due date of delivery
- Other adverse events during treatment
研究者
Brian Greenwood
Professor
London School of Hygiene and Tropical Medicine