Trial Review

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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001191381
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
30/08/2026
Date registered
Help: Date registered
24/09/2026
Date last updated
Help: Date last updated
24/09/2026
Date data sharing statement initially provided
Help: Data sharing statement date
24/09/2026
Type of registration
Help: Type of registration
Prospectively registered

Titles & IDs
Public title
Does intermittent treatment in pregnancy with sulfadoxine-pyrimethamine prevent small vulnerable newborns through non-malarial effects? - A randomised controlled trial
Scientific title
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) for prevention of small vulnerable newborns (SVN) through non-malarial mechanisms: a double-blind, placebo-controlled, superiority trial (SPARK)
Additional trial identifiers [1] 318247 0
Nil
Universal Trial Number (UTN)
Trial acronym
SPARK - Sulfadoxine-Pyrimethamine to Reduce Risks for Small Vulnerable Newborns
Related trial records

Health condition
Health condition(s) studied:
Small vulnerable newborn 343300 0
Small-for-gestational age at birth 343301 0
Preterm birth 343302 0
Condition category
Condition code
Reproductive Health and Childbirth 339418 339418 0 0
Complications of newborn
Reproductive Health and Childbirth 339419 339419 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP).

Participants randomised to the intervention arm will receive three tablets of quality-assured SP, each containing 500 mg sulfadoxine and 25 mg pyrimethamine (total dose 1500 mg sulfadoxine/75 mg pyrimethamine), taken orally as a single dose every four weeks from enrolment until delivery. SP will be administered under direct observation, repeat doses will be scheduled at four-weekly intervals, and adherence to repeat treatments will be monitored.
Intervention code [1] 335138 0
Prevention
Intervention code [2] 335139 0
Treatment: Drugs
Description of the comparator or control
Participants randomised to the control arm will receive three placebo tablets, taken orally as a single dose every four weeks from enrolment until delivery. Placebo will be administered under direct observation, repeat doses will be scheduled at four-weekly intervals, and adherence to repeat treatments will be monitored.
Control group
Placebo

Outcomes
Primary outcome [1] 346640 0
Small vulnerable newborn (SVN), defined as a live-born singleton baby who is small-for-gestational-age (SGA) and/or born preterm
Timepoint [1] 346640 0
Birth
Secondary outcome [1] 466845 0
Small-for-gestational age (SGA), defined as birthweight below the 10th centile for gestational age and infant sex based on the INTERGROWTH-21st newborn birthweight standard in a live-born singleton baby
Timepoint [1] 466845 0
Birth
Secondary outcome [2] 467102 0
Preterm birth: birth before 37+0 weeks’ gestation.
Timepoint [2] 467102 0
Birth
Secondary outcome [3] 467103 0
Composite of small vulnerable newborn, miscarriage, stillbirth, and neonatal death
Timepoint [3] 467103 0
Birth, day 28 of life
Secondary outcome [4] 467104 0
Preterm-non-SGA, defined as a live birth before 37+0 weeks' gestation with a birthweight for gestational age on or above the 10th centile on the INTERGROWTH-21st newborn birthweight standard
Timepoint [4] 467104 0
Birth
Secondary outcome [5] 467105 0
Preterm-SGA, defined as a live birth before 37+0 weeks' gestation with a birthweight for gestational age below the 10th centile on the INTERGROWTH-21st newborn birthweight standard
Timepoint [5] 467105 0
Birth
Secondary outcome [6] 467106 0
Term-SGA, defined as a live birth at or after 37+0 weeks' gestation with a birthweight for gestational age below the 10th centile on the INTERGROWTH-21st newborn birthweight standard
Timepoint [6] 467106 0
Birth
Secondary outcome [7] 467107 0
Birthweight
Timepoint [7] 467107 0
Birth
Secondary outcome [8] 467108 0
Birthweight z-score
Timepoint [8] 467108 0
Birth
Secondary outcome [9] 467109 0
Gestational age at birth
Timepoint [9] 467109 0
Birth
Secondary outcome [10] 467110 0
Newborn length
Timepoint [10] 467110 0
Birth
Secondary outcome [11] 467111 0
Newborn abdominal circumference
Timepoint [11] 467111 0
Birth
Secondary outcome [12] 467112 0
Newborn head circumference
Timepoint [12] 467112 0
Birth
Secondary outcome [13] 467113 0
Infant length z-score
Timepoint [13] 467113 0
Six weeks of life
Secondary outcome [14] 467114 0
Infant weight z-score
Timepoint [14] 467114 0
Six weeks of life
Secondary outcome [15] 467115 0
Maternal haemoglobin
Timepoint [15] 467115 0
30 gestational weeks, birth
Secondary outcome [16] 467116 0
Maternal gestational weight gain
Timepoint [16] 467116 0
Antenatal study visits, scheduled in 4-week intervals from enrolment into the trial.
Secondary outcome [17] 467117 0
Maternal body mass index
Timepoint [17] 467117 0
30 gestational weeks
Secondary outcome [18] 467118 0
Maternal mid-upper arm circumference
Timepoint [18] 467118 0
30 gestational weeks
Secondary outcome [19] 467119 0
Congenital abnormality
Timepoint [19] 467119 0
Birth, six weeks postpartum
Secondary outcome [20] 467120 0
Maternal death
Timepoint [20] 467120 0
From enrolment to six weeks postpartum
Secondary outcome [21] 467121 0
Grade 3-5 adverse events (maternal)
Timepoint [21] 467121 0
From first administration of study intervention to six weeks postpartum
Secondary outcome [22] 467122 0
Grade 3-5 adverse events (infant)
Timepoint [22] 467122 0
From birth to day 28, in live births.
Secondary outcome [23] 467123 0
Fetal loss (miscarriage, stillbirth)
Timepoint [23] 467123 0
Birth
Secondary outcome [24] 467124 0
Vomiting within 30 minutes of study drug administration
Timepoint [24] 467124 0
From administration of study intervention to 30 minutes after administration, for each dose
Secondary outcome [25] 467125 0
Vomiting within 24 hours of study drug administration
Timepoint [25] 467125 0
From administration of study intervention to 24 hours after administration, for each dose
Secondary outcome [26] 467126 0
Nausea within 24 hours of study drug administration
Timepoint [26] 467126 0
From administration of study intervention to 24 hours after administration, for each dose
Secondary outcome [27] 467127 0
Other symptoms (not nausea and/or vomiting) within 24 hours of study drug administration
Timepoint [27] 467127 0
From administration of study intervention to 24 hours after administration, for each dose

Eligibility
Key inclusion criteria
- Viable singleton intrauterine pregnancy
- Estimated gestational age between 14-20 weeks as confirmed by ultrasound
- Agreed to stay in the study area up to delivery and postpartum follow-up
- 16 years of age or older
- Willing to adhere to scheduled and unscheduled study visit procedures
- Willing to birth in a study health centre or hospital
- Able to provide written informed consent
Minimum age
16 Years
Maximum age
No limit
Sex
Females
Healthy volunteers
No
Key exclusion criteria
- Multiple pregnancy (e.g., twins/triplets)
- Known heart ailment or chronic medical condition requiring frequent medical attention
- Active medical problem requiring inpatient evaluation at the time of screening
- Major foetal malformations or non-viable pregnancy if observed on dating ultrasound
- Known allergy or contraindication to study drugs or their active components
- Early or active labour (documented by cervical change with uterine contractions)
- Haemoglobin at screening below 5 g/dL

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Computer-based central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be computer-generated using permuted blocks of varying sizes and stratified by study area.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A total of 600 pregnant women (300 per treatment arm) will be randomised. This provides 80% power to detect a 30% reduction in the risk of the primary outcome, SVN, from 40.0% in the placebo arm to 28.0% in the IPTp-SP arm, using a two-sided alpha of 0.05 and allowing for 18.5% attrition.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2026
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment outside Australia
Country [1] 28460 0
Bangladesh
State/province [1] 28460 0
Mirpur and Korail settlements in Dhaka

Funding & Sponsors
Funding source category [1] 322800 0
Charities/Societies/Foundations
Name [1] 322800 0
Thrasher Research Fund
Country [1] 322800 0
United States of America
Funding source category [2] 322806 0
Charities/Societies/Foundations
Name [2] 322806 0
Cures Within Reach
Country [2] 322806 0
United States of America
Primary sponsor type
University
Name
Menzies School of Health Research
Address
Country
Australia
Secondary sponsor category [1] 325729 0
Charities/Societies/Foundations
Name [1] 325729 0
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b)
Address [1] 325729 0
Country [1] 325729 0
Bangladesh

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321240 0
The Human Research Ethics Committee (HREC) of the Northern Territory (NT) Department of Health and Menzies School of Health Research
Ethics committee address [1] 321240 0
Ethics committee country [1] 321240 0
Australia
Date submitted for ethics approval [1] 321240 0
23/02/2026
Approval date [1] 321240 0
23/07/2026
Ethics approval number [1] 321240 0
2026-5361
Ethics committee name [2] 321247 0
icddr,b Ethical Review Committee
Ethics committee address [2] 321247 0
Ethics committee country [2] 321247 0
Bangladesh
Date submitted for ethics approval [2] 321247 0
07/04/2026
Approval date [2] 321247 0
17/05/2026
Ethics approval number [2] 321247 0
PR-26-007

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 153118 0
A/Prof Holger Unger
Address 153118 0
Menzies School of Health Research Darwin, John Mathews Building, Royal Darwin Hospital Campus, 58 Rocklands Dr, Tiwi, NT 0810, Australia
Country 153118 0
Australia
Phone 153118 0
+61 474210702
Fax 153118 0
Email 153118 0
[email protected]
Contact person for public queries
Name 153119 0
Dr Anisur Rahman
Address 153119 0
International Centre for Diarrheal Disease Research, Bangladesh 68, Shaheed Tajuddin Ahmed Sarani, Mohakhali Dhaka 1212, Bangladesh
Country 153119 0
Bangladesh
Phone 153119 0
+880 2 222277001
Fax 153119 0
Email 153119 0
[email protected]
Contact person for scientific queries
Name 153120 0
Holger Unger
Address 153120 0
Menzies School of Health Research Darwin, John Mathews Building, Royal Darwin Hospital Campus, 58 Rocklands Dr, Tiwi, NT 0810, Australia
Country 153120 0
Australia
Phone 153120 0
+61 474210702
Fax 153120 0
Email 153120 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• No requirements
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Data repository: https://www.iddo.org/wwarn

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.