Establishing Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy

NCT01053325 | Completed Phase 3 DMC

• 1 other identifier: ITMP0409
• Study Type: interventional
• Target: 848
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Malaria in Pregnancy; HIV Infections

Keywords

Malaria; Pregnancy; Prevention; HIV; Sub-Sahara Africa

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to the end of pregancy

Secondary Outcomes (4)

• 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/µl

  Up to the end of pregnancy

• To 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

  Up to the end of pregnancy

• 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

  At delivery

• 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

  Up to the end of pregancy

Study Arms (5)

CTX in HIV-negative women

EXPERIMENTAL

CTX daily prophylaxis in HIV-negative pregnant women

Drug: Cotrimoxazole prophylaxis

CTX in HIV-positive women

EXPERIMENTAL

CTX daily prophylaxis in pregnant women who are infected with HIV

Drug: Cotrimoxazole prophylaxis

SP IPT in HIV-negative women

ACTIVE COMPARATOR

Intermittent Preventive Treatment with SP in HIV-negative pregnant women

Drug: SP IPT

IPT SP in HIV-positive women

ACTIVE COMPARATOR

Intermittent Preventive Treatment with SP in HIV-positive pregnant women

Drug: SP IPT

CTX in HIV-positive pregnant women with CD4<350

ACTIVE COMPARATOR

Daily prophylaxis with cotrimoxazole in HIV-positive pregnant women with CD4\<350

Drug: Cotrimoxazole prophylaxis

Interventions

Cotrimoxazole prophylaxis DRUG

Daily prophylaxis with cotrimoxazole

Also known as: CTX, Bacrtim (R)

CTX in HIV-negative women; CTX in HIV-positive pregnant women with CD4<350; CTX in HIV-positive women

SP IPT DRUG

Intermittent preventive treatment with sulphadoxine-pyrimethamine

Also known as: SP, Fansidar (R)

IPT SP in HIV-positive women; SP IPT in HIV-negative women

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Tropical Diseases Research Centre, Zambia: collaborator

Study Sites (1)

Kabuta Health Centre

Kabuta, Nchelenge District, Luapula Province of, Zambia

Location

MeSH Terms

Conditions

HIV Infections; Malaria

Interventions

fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Christine Manyando, MD

  Tropical Diseases Research Centre, Zambia

  PRINCIPAL INVESTIGATOR

• Umberto D'Alessandro, MD, PhD

  Insitute of Tropical Medicine, Antwerp, Belgium

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2010
• First Posted: January 21, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2013
• Last Updated: October 24, 2013

Record last verified: 2013-10

Locations

ZA (1)