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Brief Title † | Intermittent Preventive Treatment (IPTp) Versus Rapid Diagnostic Testing (RDT) and Treatment of Malaria in Pregnancy | ||||||||||||||||||||
Official Title † | The Effectiveness, Cost and Cost Effectiveness of Intermittent Preventive Treatment or Screening and Treatment of Malaria in Pregnancy Among Women Using Long Lasting Insecticide Treated Bed Net: a Randomised Controlled Trial. | ||||||||||||||||||||
Brief Summary | Among the best practices recommended for malaria control during pregnancy is ensuring effective case management of malaria illness. However, this is often not practiced because (1) malaria infection in pregnancy is often asymptomatic, (2) peripheral parasitaemia may be absent even when the placenta is heavily parasitized, (3) implementing diagnosis and treatment of malaria within a routine antenatal service may be difficult and (4) antimalarial treatment options available to pregnant women are limited due to resistance to chloroquine(CQ) and sulfadoxine-pyrimethamine(SP0 and paucity of safety and efficacy data on other antimalarial drugs in pregnancy, particularly artemisinin combination treatments (ACT). Therefore the commonest recommended practice in pregnancy is the administration of SP as intermittent preventive treatment (SP-IPTp). However, the effectiveness of SP-IPTp has been questioned because parasite resistance to SP is spreading rapidly across sub-Saharan Africa. This is a three-arm open label randomised control non-inferiority trial of insecticide-treated nets(ITN) plus rapid diagnostic test(RDT) screening, and treatment with SP or amodiaquine plus artimisinin(AQ+AS) versus ITN plus IPTp using SP. It is to be carried out in pregnant women of all parities presenting at enrolling antenatal clinics with a gestation of 16 to 20 weeks at their first booking. The key objectives are to demonstrate that (1) the prevalence of severe anaemia (Hb < 8g/dl) at 34 to 36 weeks of gestation (2) the prevalence of low birth weight (BW < 2500g) at delivery or within 72 hours after delivery (3) the prevalence of placenta parasitaemia and (4) the incidence of serious and non-serious adverse events in the ITN plus RDT screening and treatment arm are not greater than those in the ITN plus IPTp arm. Alongside the clinical assessments, health care cost assessments will be done to determine the cost-effectiveness of the two delivery strategies measured as cases of severe maternal anaemia averted. |
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Detailed Description | General objective To show that the long-lasting insecticide-treated nets(LLIN)///// plus RDT screening and treatment strategy is not inferior to LLIN plus SP-IPTp in reducing the burden of malaria during pregnancy. Specific objectives Primary 1. To demonstrate that the prevalence of severe anaemia (Hb < 8g/dl) at 34 to 36 weeks of gestation in the LLIN plus RDT screening and case management arm is not greater than that in the LLIN plus IPTp arm. Secondary
Sample size The prevalences of severe anaemia at delivery and low birth weight have been shown to be 12% and 5.7% respectively among Gambian multigravidae who received varying doses of SP-IPT (Mbaye et al. 2006). In the absence of local data from the proposed study site, we estimate that the prevalences of severe anaemia in the third trimester and low birth weight will be 12% and 6% respectively in the LLIN +SP-IPTp arm of this study, similar to that in the Gambian population. For trial planning we have set a non-inferiority margin of 5%. This means we would consider the LLIN + RDT screening with SP or AQ+AS treatment options to be inferior to the LLIN +SP-IPTp option if the prevalence of severe anaemia at 34 to 36 weeks is 5% greater in the LLIN+RDT with SP or AS+AQ treatment arm than that is observed in the LLIN+SP-IPT arm. Since we expect the prevalence of severe anaemia in the LLIN +SP-IPTp arm would be 12%, we need 887 women per arm to detect a 5% difference between the two study arms at 95% significance with 90% power. Considering a 20% dropout rate we need 1110 women per arm. Setting a non-inferiority margin of 5% seems clinically and statistically relevant; and yields a sample size that makes the execution of the study feasible within the time frame and with the resources available. Choosing a smaller margin than 5% may be too tight requiring large sample size of over 2000 per arm which might not be feasible and achievable within the time frame; a larger margin than 5% may be too liberal to compare the public health impact of these interventions. We estimate that 925 women per arm can show with 90% power at 95% significance level and accounting for a 20% dropout rate, that the prevalence of low birth weight associated with the LLIN + RDT screening with or without SP or AQ+AS treatment is no worse than LLIN + SP-IPTp by a margin of 4%. Since, a sample size of 1110 per arm is adequate to detect any effects of the interventions on both birth weight and maternal Hb, a total of 3330 pregnant women will be recruited into this study. Study Design A three-arm open label randomised control non-inferiority trial of RDT screening with or without treatment with SP or AQ+AS versus IPTp using SP as follows: -
Study site and population The study will be conducted in the Ejisu-Juaben and Sekyere East districts of the Ashanti Region of Ghana. Enrolment will be done simultaneously at the antenatal clinics of the Effiduase and Juaben district hospitals and a sub district health centre in each of the districts. The Effiduase and Juaben hospitals have 50 and 40 beds respectively and provide all basic medical services including adult medicine, paediatrics, surgery and obstetrics and gynaecology. They run weekly antenatal clinic sessions and together they register an average of 220 new pregnant women per month. The sub district health centres (at Kwaso and Kumawu) are manned by qualified medical assistants and midwives. Together they register an average of 80 new pregnant women per month. All health facilities in the study districts including the proposed enrolling clinics offer SP-IPT to pregnant women following the MoH guidelines. Pregnant women in their second or third trimester diagnosed with malaria are treated with AQ+AS as recommended by the MoH at these facilities. The study population will comprise pregnant women presenting at the hospital's antenatal clinic with a gestation of 16 to 24 weeks at their first booking. Enrolment Procedures A schematic profile of the study is shown in Figure 1. All study women will be recruited from weekly antenatal clinic sessions held at the study sites over a period of one and half years. Three teams of midwives and their assistants put together and trained by the principal investigator (PI) will assist the PI and research teams to conduct the recruitment during antenatal clinic hours. The standard operating procedures at the clinic will be as follows:
Antenatal Follow-Up Procedures
Delivery and Postpartum Follow-up
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Study Phase | Phase III | ||||||||||||||||||||
Study Type † | Interventional | ||||||||||||||||||||
Study Design † | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study | ||||||||||||||||||||
Primary Outcome Measure † | Prevalence of severe maternal anaemia (Hb < 8g/dl) at 34 to 36 weeks of gestation. [ Time Frame: At 34 to 36 weeks of gestation ] [ Designated as safety issue: Yes ] | ||||||||||||||||||||
Secondary Outcome Measure † | Prevalence of low birth weight (BW < 2500g) at delivery or within 72 hours of delivery. [ Time Frame: At delivery or within 72 hours of delivery. ] [ Designated as safety issue: Yes ] Prevalence of maternal anaemia (Hb < 11g/dl) at 34 to 36 weeks of gestation. [ Time Frame: At 34 to 36 weeks of gestation ] [ Designated as safety issue: Yes ] Prevalence of placenta parasitaemia. [ Time Frame: At delivery ] [ Designated as safety issue: Yes ] Incidence of post-intervention malaria cases [ Time Frame: Anytime after enrolment and prior to delivery ] [ Designated as safety issue: Yes ] Proportions of congenital anomalies in live births among the intervention groups stratified by gestation, gravidity, parity and age. [ Time Frame: At delivery ] [ Designated as safety issue: Yes ] Proportions of spontaneous abortions, intrauterine death, stillbirths, neonatal and maternal mortality and pre-term deliveries. [ Time Frame: Anytime after enrolment and prior to delivery ] [ Designated as safety issue: Yes ] Cost per severe maternal anaemia averted. [ Time Frame: Anytime after enrolment and prior to delivery ] [ Designated as safety issue: No ] Cost per (non-severe) maternal anaemia averted. [ Time Frame: Anytime after enrolment and prior to delivery ] [ Designated as safety issue: No ] Cost per peripheral malaria case averted. [ Time Frame: Anytime after enrolment and prior to delivery ] [ Designated as safety issue: No ] Cost per placental malaria averted. [ Time Frame: At delivery ] [ Designated as safety issue: No ] |
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Condition † | Malaria Anaemia Pregnancy |
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Intervention † | Drug: Amodiaquine plus artesunate combination; sulphadoxine-pyrimethamine | ||||||||||||||||||||
MEDLINE PMIDs | |||||||||||||||||||||
Links | Sponsor Website  | ||||||||||||||||||||
Recruitment Information Fields | |||||||||||||||||||||
Recruitment Status † | Recruiting | ||||||||||||||||||||
Enrollment † | 3330 | ||||||||||||||||||||
Start Date † | February 2007 | ||||||||||||||||||||
Estimated Completion Date | June 2009 | ||||||||||||||||||||
Estimated Primary Completion Date | December 2008 (final data collection date for primary outcome measure) | ||||||||||||||||||||
Eligibility Criteria † | Inclusion Criteria:
Exclusion Criteria:
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Gender | Female | ||||||||||||||||||||
Ages | |||||||||||||||||||||
Accepts Healthy Volunteers | No | ||||||||||||||||||||
Contacts †† |
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Location Countries † | Ghana | ||||||||||||||||||||
Administrative Information Fields | |||||||||||||||||||||
NCT ID † | NCT00432367 | ||||||||||||||||||||
Organization ID | GMP_REG04 | ||||||||||||||||||||
Secondary IDs †† | HKT-GMP | ||||||||||||||||||||
Study Sponsor † | Gates Malaria Partnership | ||||||||||||||||||||
Collaborators †† | Kwame Nkrumah University of Science and Technology | ||||||||||||||||||||
Investigators † |
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Information Provided By | Gates Malaria Partnership | ||||||||||||||||||||
Verification Date | February 2008 | ||||||||||||||||||||
First Received Date † | February 5, 2007 | ||||||||||||||||||||
Last Updated Date | February 7, 2008 |