Establishing Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy
Information source: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Malaria in Pregnancy; HIV Infections
Intervention: Cotrimoxazole prophylaxis (Drug); SP IPT (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Institute of Tropical Medicine, Belgium Official(s) and/or principal investigator(s): Christine Manyando, MD, Principal Investigator, Affiliation: Tropical Diseases Research Centre, Zambia Umberto D'Alessandro, MD, PhD, Study Director, Affiliation: Insitute of Tropical Medicine, Antwerp, Belgium
Summary
Malaria is a major contributor of disease burden in Sub-Saharan Africa: 90% of global cases
occur there, and pregnant women and children under 5 years are the most vulnerable. Malaria
in pregnancy increases risks of abortion, stillbirth, prematurity, intrauterine growth
retardation and maternal anemia, and is associated with higher risk of low birth weight and
perinatal, neonatal and infant mortality. For prevention and control of malaria in
pregnancy, the WHO recommends Intermittent Preventive Treatment (IPT) with antimalarial
drugs, insecticide treated nets (ITNs) and effective treatment of malaria and anemia.
HIV in pregnancy increases the risks of malaria, and it seems that the efficacy of IPT with
the drug sulphadoxine-pyrimethamine (SP) is decreased in HIV+ pregnant women.
Malaria prevention in pregnancy in Zambia relies on ITNs and IPT with SP. Daily prophylaxis
with cotrimoxazole (CTX) effectively reduces mortality and morbidity in HIV+ individuals,
and antibiotic therapy during pregnancy might help to decrease adverse pregnancy outcomes.
CTX prophylaxis improves birth outcomes in HIV+ women with CD4<200/µl: a study concluded
that antenatal provision of CTX was beneficial for HIV+ pregnant women with low CD4 but not
in women with ≥200/µl (however, this study was carried out in an area with very low risk of
malaria , and CTX may have a different effect depending on endemic conditions). The WHO
recommends daily CTX in addition to ARVs, to prevent opportunistic infections in all HIV+
patients.
Concurrent administration of SP and CTX may increase the incidence of severe adverse
reactions in HIV+ patients, so WHO has promoted CTX prophylaxis as an alternative to SP for
the IPT in immuno-compromised pregnant women. Unfortunately, there is insufficient
information on the effectiveness of daily CTX for preventing malaria infection in pregnancy:
so, SP is still the only antimalarial recommended by WHO for this purpose. With the increase
in SP resistance and with the newer antimalarials still being studied for safety and
efficacy in pregnancy, CTX could be an alternative for SP in reducing malaria and
malaria-related morbidity and mortality in pregnancy.
This study will try to to see if in HIV- and HIV+ pregnant women, CTX is not inferior to SP
in reducing placental parasitaemia. Such information is needed to issue updated, effective
guidelines on malaria prevention in pregnancy
Clinical Details
Official title: A Clinical Trial to Establish The Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: To establish that in HIV negative pregnant women co-trimoxazole prophylaxis is non inferior to SP IPT with respect to birth weight at delivery (or within 24 hours). Non inferiority is defined as a difference in mean birth weights of no more than 100g.
Secondary outcome: To evaluate the effectiveness of co-trimoxazole prophylaxis and SP IPT in reducing placenta malaria in HIV+ pregnant women with CD4 ≥ 350/µl and in the combined group of HIV- and HIV+ pregnant women with CD4 ≥ 350/µlTo evaluate the effectiveness of CTX and SP IPT in reducing malaria peripheral infection, in HIV negative, and in HIV positive pregnant women with a CD4 cell count ≥ 350/µl To evaluate the effect of CTX and SP IPT on the offspring by measuring the gestational age at delivery, perinatal mortality and birth weight, in HIV negative pregnant women and in HIV positive pregnant women with a CD4 cell count ≥ 350/µl To compare the effectiveness and safety profiles of CTX prophylaxis to that of SP IPT, in HIV negative pregnant women and in HIV positive pregnant women with a CD4 cell count ≥ 350/µl
Detailed description:
Malaria is a major contributor of the disease burden in Sub-Saharan Africa: some 90% of
global cases occur in Sub-Saharan Africa, with pregnant women and children < 5 representing
the most vulnerable population. P. falciparum infection in pregnancy leads to parasite
sequestration in the maternal placental vascular space, causing increased risks of abortion,
stillbirth, prematurity, intrauterine growth retardation and maternal anaemia; it is also
associated with increased risk of low birth weight (LBW) and perinatal, neonatal and infant
mortality. In low transmission areas, malaria can be severe with a high risk of maternal and
perinatal mortality (up to 60-70%). In highly endemic areas, malaria is still associated
with maternal anaemia, LBW and stillbirth. For prevention and control of malaria in
pregnancy, the WHO recommends Intermittent Preventive Treatment (IPT), insecticide treated
nets (ITNs) and effective case management for malaria and anaemia.
HIV-1 infection in pregnancy increases the risks of malaria. In HIV+ pregnant women, in
addition, the efficacy of IPT with sulphadoxine-pyrimethamine (SP) appears decreased.
In Zambia, the malaria incidence rate increased from 121. 5/1000 in 1976 to 482. 0/1000 in
2003. The high rates were predominantly evident among pregnant women and children
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Confirmed pregnancy (through palpable fundus and/ or positive pregnancy test)
- Gestational age between 16 and 28 weeks
- Hb > 7 g/dl, by Hemocue
- No symptoms consistent with malaria
- Residence within the health facility catchment's area
- Willingness to deliver at the health facility
- Willingness to adhere to all requirements of the study (including HIV-1 voluntary
counselling and testing)
- Ability to provide written informed consent. If the woman is a minor of age/not
emancipated, the consent must be given by a parent or legal guardian according to
national law (however, in this case, also the minor woman will sign the consent form,
to document that she is freely giving her assent to take part in the study).
Exclusion Criteria:
- History of allergy to study drugs, or previous history of allergy to sulpha drugs
- History or presence of major illnesses likely to influence pregnancy outcome
including diabetes mellitus, severe renal or heart disease, or active tuberculosis
- Any significant illness at the time of screening that requires hospitalization
- Intent to move out of the study's catchment area before delivery or deliver at
relative's home out of the catchment's area;
- Prior enrolment in the study or concurrent enrolment in another study
- Severe anaemia (Hb<7 g/dl)
- Previous history of unfavourable pregnancy outcome: pre-eclampsia, caesarean section,
stillbirth.
- Eligible HIV-positive women who, following the National guidelines, have to be put on
CTX prophylaxis (e. g. having a CD4 count <350/µl) or already on CTX and/or ARV
treatment will be excluded from the RCT but included in a prospective observational
cohort and receive 2 tablets of CTX daily
Locations and Contacts
Kabuta Health Centre, Kabuta, Nchelenge District, Luapula Province of, Zambia
Additional Information
Starting date: September 2010
Last updated: October 23, 2013
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