Intermittent Preventive Treatment Versus Scheduled Screening and Treatment of Malaria in Pregnancy (IPTp_IST)

• ClinicalTrials.gov Identifier: NCT01084213
• Recruitment Status: Completed
• First Posted: March 10, 2010
• Last Update Posted: April 11, 2014
• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Medical Research and Training Centre, Mali; University of Ouagadougou, Burkina Faso; Medical Research Council Unit, The Gambia; Navrongo Health Research Centre, Ghana; Liverpool School of Tropical Medicine
• Information provided by (Responsible Party): London School of Hygiene and Tropical Medicine

Tracking Information

• First Submitted Date: March 3, 2010
• First Posted Date: March 10, 2010
• Last Update Posted Date: April 11, 2014
• Study Start Date: June 2010
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2010)

• Prevalence of low birth weight [ Time Frame: 6 - 18 months ]
• Prevalence of third trimester anaemia [ Time Frame: 3 - 12 months ]
• Prevalence of placenta malaria [ Time Frame: 6 - 18 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 8, 2010)

• Prevalence of anaemia at the time of delivery or shortly afterwards. [ Time Frame: 6 - 18 months ]
• Prevalence of peripheral blood parasitaemia [ Time Frame: 6 - 18 months ]
• Episodes of clinical malaria during the course of the pregnancy. [ Time Frame: 1 year ]
• Serious adverse events in the mother. [ Time Frame: 6 - 18 months ]
• Adverse outcome of pregnancy - abortions, still births and neonatal deaths. [ Time Frame: 6 - 18 months ]
• Occurrence of congenital abnormalities. [ Time Frame: 6 - 18 months ]
• Feasibility and costs of each approach to the control of malaria in pregnancy. [ Time Frame: 1 year ]
• Cost per cases of maternal anaemia (severe and non-severe) and peripheral malaria averted. [ Time Frame: 1 year ]
• Acceptability of each approach by pregnant women and antenatal clinic staff. [ Time Frame: 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intermittent Preventive Treatment Versus Scheduled Screening and Treatment of Malaria in Pregnancy
• Official Title: A Trial of Intermittent Preventive Treatment With Sulfadoxine-pyrimethamine Versus Intermittent Screening and Treatment of Malaria in Pregnancy

Brief Summary

The incidence of malaria, including the incidence in pregnant women, is declining in many African countries. Thus, there is a need to re-examine the efficacy and cost effectiveness of giving intermittent preventive treatment with sulphadoxine-pyrimethamine in pregnancy (SP-IPTp) on several occasions during pregnancy, an intervention that is threatened by increasing resistance to SP. Possible alternatives to SP-IPTp need to be explored. This applies especially to areas with highly seasonal malaria transmission where women are at risk for only a short period of the year.

The goal of this project is to determine whether in pregnant women who sleep under a long lasting insecticide treated bed net, screening and treatment at each scheduled antenatal clinic visit is as effective in protecting them from anaemia, low birth weight and placental infection as SP-IPTp.

Primigravidae and secundigravidae who present at antenatal clinics in study sites in four West African countries (Burkina Faso, Ghana, Mali and The Gambia) will be randomised to one of two groups. All women will be given a long lasting insecticide treated bed net on first presentation at the antenatal clinic. Women in group 1 (reference group) will receive SP-IPTp according to the current WHO guidelines. Those in group 2 will be screened with a rapid diagnostic test at each scheduled antenatal clinic visit and treated if parasitaemic. Approximately 5000 women will be recruited, 2500 in each group. Women will be encouraged to deliver in hospital where maternal haemoglobin and birth weight will be recorded and a placental sample obtained. Those who deliver at home will be visited within a week of delivery and maternal haemoglobin and infant weight recorded. Mothers and infants will be seen again six weeks after delivery. Also at delivery peripheral maternal blood sample will be obtained for the diagnosis of malaria using RDT, microscopy and PCR. The primary end points of the trial will be birth weight and anaemia at 38 weeks (+/-2 weeks) of gestation. The study is powered to show non-inferiority of group 2 compared to group 1. The costs and cost effectiveness of each intervention will be evaluated.

In the light of recent evidence suggesting that malaria infection during pregnancy, particularly in the last trimester may influence an infant's risk of malaria, we proposed to follow infants born to mothers recruited in the Navrongo site in Ghana who have received either IST or IPTp in pregnancy throughout the whole of their first year of life beyond the six weeks originally proposed. We have received approval for this from the ethic committees at Kwame Nkrumah University of Science and Technology, Ghana Health Service and Navrongo Health Research Centre. The aim is to obtain information on the incidence of both symptomatic and asymptomatic malaria infections in these infants during follow up of the infants.

The study will provide information to national malaria control programmes on whether there are alternative, safe and effective methods to the SP IPTp regimen for reducing the burden of malaria in pregnancy.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Health Services Research

Condition

• Malaria
• Pregnancy
• Anaemia

Intervention

• Drug: Intermittent screening and treatment of malaria in pregnancy (IST)
  Scheduled intermittent screening of study women using rapid diagnostic test and treatment of those who are RDT positive during ante-natal clinic visits in the 2nd and 3rd trimester with arthemether lumefantrine.
  Other Name: Coartem
• Drug: SP-IPTp
  Study women will receive at least two doses of Sulfadoxine Pyrimethamine during their pregnancy, one at each of the recommended ante-natal visits during the 2nd and 3rd trimester.
  Other Name: SP

Study Arms

• Active Comparator: IPTp with SP
  Study women will receive at least two doses of SP during their pregnancy, one at each of the recommended ante-natal visits during the 2nd and 3rd trimester.
  Intervention: Drug: SP-IPTp
• Experimental: IST using RDTs
  Scheduled intermittent screening using rapid diagnostic tests and treatment of those who are RDT positive during ante-natal clinic visits in the 2nd and 3rd trimester.
  Intervention: Drug: Intermittent screening and treatment of malaria in pregnancy (IST)

Publications *

• Berry I, Walker P, Tagbor H, Bojang K, Coulibaly SO, Kayentao K, Williams J, Oduro A, Milligan P, Chandramohan D, Greenwood B, Cairns M. Seasonal Dynamics of Malaria in Pregnancy in West Africa: Evidence for Carriage of Infections Acquired Before Pregnancy Until First Contact with Antenatal Care. Am J Trop Med Hyg. 2018 Feb;98(2):534-542. doi: 10.4269/ajtmh.17-0620. Epub 2017 Nov 30.
• Tagbor H, Cairns M, Bojang K, Coulibaly SO, Kayentao K, Williams J, Abubakar I, Akor F, Mohammed K, Bationo R, Dabira E, Soulama A, Djimdé M, Guirou E, Awine T, Quaye S, Njie F, Ordi J, Doumbo O, Hodgson A, Oduro A, Meshnick S, Taylor S, Magnussen P, ter Kuile F, Woukeu A, Milligan P, Chandramohan D, Greenwood B. A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy. PLoS One. 2015 Aug 10;10(8):e0132247. doi: 10.1371/journal.pone.0132247. eCollection 2015.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 10, 2014): 5354
• Original Estimated Enrollment (submitted: March 8, 2010): 5000
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Presence of a first or second pregnancy.
2. Gestation between 16 to 30 weeks inclusive at first booking as determined by symphysio-fundal measurements.
3. Provision of informed consent to join the trial.
4. Residence in the study area and intention to stay in the area for the duration of the pregnancy.

Exclusion Criteria:

1. Absence of informed consent.
2. An intention to leave the study area before delivery.
3. A history of sensitivity to sulphonamides.
4. Clinical AIDS or known HIV positivity.
5. Presence of any systemic illness likely to interfere with interpretation of the results of the trial.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 16 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Burkina Faso, Gambia, Ghana, Mali

Administrative Information

• NCT Number: NCT01084213
• Other Study ID Numbers: MiPcMA05
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: London School of Hygiene and Tropical Medicine
• Study Sponsor: London School of Hygiene and Tropical Medicine

Collaborators

• Medical Research and Training Centre, Mali
• University of Ouagadougou, Burkina Faso
• Medical Research Council Unit, The Gambia
• Navrongo Health Research Centre, Ghana
• Liverpool School of Tropical Medicine

Investigators

• Principal Investigator: Brian Greenwood, MD; London School of Hygiene & Tropical Medicine, UK.
• Principal Investigator: Daniel Chandramohan, PhD; London School of Hygiene & Tropical Medicine, UK.
• Principal Investigator: Paul Milligan, PhD; London School of Hygiene & Tropical Medicine, UK.
• Principal Investigator: Feiko T Kuile, PhD; Liverpool School of Tropical Medicine, UK
• Principal Investigator: Harry Tagbor, DrPH; Kwame Nkrumah University of Science & Technology, School of Medical Sciences, Ghana

• PRS Account: London School of Hygiene and Tropical Medicine
• Verification Date: April 2014