ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618000216213

Ethics application status

Approved

Date submitted

1/02/2018

Date registered

9/02/2018

Date last updated

24/02/2023

Date data sharing statement initially provided

30/04/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Prolong: a double-blind randomised placebo-controlled trial of broccoli sprout extract in
women with early onset preeclampsia.

Scientific title

Randomised controlled trial of broccoli sprout extract targeting gestational length in women with early onset preeclampsia

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1205-0293

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

preeclampsia

Condition category

Condition code

Reproductive Health and Childbirth

Fetal medicine and complications of pregnancy

Cardiovascular

Hypertension

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The oral consumption of 8 broccoli seed extract capsules (64mg) twice a day for the remainder of pregnancy once diagnosed with early onset preeclampsia.
Minimum duration is 48 hours with no maximum duration.
Adherence will be monitored via a self administered drug diary.

Intervention code [1]

Treatment: Other

Comparator / control treatment

The control will be a delayed release placebo capsule comprising of hydroxypropylmethylcellulose.

Control group

Placebo

Outcomes

Primary outcome [1]

The interval between enrolment and delivery, recorded in days.

Timepoint [1]

Primary timepoint will be measured from the initiation of treatment until delivery. Hospital records will be used to generate this information.

Secondary outcome [1]

Composite maternal outcome including maternal death, eclampsia, HELLP syndrome , pulmonary oedema , thromboembolic event (significant deep vein thrombosis or pulmonary embolus), placental abruption , major postpartum haemorrhage , severe renal impairment , liver haematoma or rupture.

Timepoint [1]

Will be measured from 24 hours prior to initiation of treatment, and then every 48 hours after treatment is initiated until delivery. Additional information regarding clinical outcomes of eclampsia, HELLP syndrome , pulmonary oedema , thromboembolic event (significant deep vein thrombosis or pulmonary embolus), placental abruption , major postpartum haemorrhage , severe renal impairment , liver haematoma or rupture will be sourced from medical records.

Secondary outcome [2]

Composite neonatal outcomes, including neonatal death before hospital discharge, 5 minute APGAR score <7, umbilical lactate >5.0 at birth, admission to the neonatal intensive care unit, diagnosis of respiratory distress syndrome, bronchopulmonary dysplasia , sepsis, necrotising enterocolitis, intraventricular haemorrhage (grade III or IV), stage 4 or 5 retinopathy of prematurity, as determined by the treating clinician.

Timepoint [2]

Will be measured on the day of delivery and information regarding routine markers will be sourced from the Neonatal Intensive Care Unit and Special Care Nursery records.

Secondary outcome [3]

Maternal serum and placental angiogenic markers sFlt-1, soluble endoglin, placental growth factor and activin A.

Timepoint [3]

Will be measured in the maternal blood 24 hours prior to initiation of treatment, and then every 48 hours after treatment is initiated until delivery.

Secondary outcome [4]

Maternal TSH and free and total T3/T4 (measured at baseline and after delivery).

Timepoint [4]

Maternal thyroid function assessed by measuring T3/T4 and TSH will be measured on enrolment and at delivery through routine pathology services from serum and/or plasma collected as part of this trial.

Secondary outcome [5]

Preeclampsia severity, as assessed by: escalation of antihypertensive therapy, systolic and diastolic blood pressures, severe renal involvement (serum or plasma creatinine >90umol/L, oliguria <80mL/4hr), haematological involvement (haemolysis , platelets <104/uL, disseminated intravascular coagulation) liver transanimases >500IU.

Timepoint [5]

These features of preeclampsia will be measured throughout pregnancy as part of routine care. Information will be sourced from routine medical records after delivery.

Secondary outcome [6]

Indication for delivery (maternal or fetal compromise).

Timepoint [6]

This will be established from routine medical records after delivery.

Secondary outcome [7]

Mode of labour and birth (prelabour caesarean section, intrapartum caesarean section, induced or spontaneous labour, spontaneous vaginal birth, assisted vaginal birth).

Timepoint [7]

Information regarding mode of birth will be sourced from routine medical records after delivery

Secondary outcome [8]

Intrauterine fetal death (stillbirth).

Timepoint [8]

Fetal wellbeing will be recorded throughout pregnancy in routine medical records. Information regarding fetal death will be sourced from medical records.

Secondary outcome [9]

Changes in fetal surveillance (fetal Doppler studies – umbilical or middle cerebral artery PI or abnormal ductus venosus – amniotic fluid volume <5cm, abnormal fetal heart rate on CTG).

Timepoint [9]

Fetal surveillance will be conducted throughout pregnancy of women with early onset preeclampsia as part of routine care. Abnormalities in fetal surveillance will be determined from routine medical records.

Secondary outcome [10]

Gestation at birth.

Timepoint [10]

This will be sourced from routine medical records after delivery.

Secondary outcome [11]

Duration of NICU care (days)

Timepoint [11]

Information regarding length of stay in NICU will be sourced from neonatal medical records after discharge from hospital.

Secondary outcome [12]

Birthweight <5th percentile.

Timepoint [12]

Information regarding birthweight will be sourced from online records. This will be done after delivery.

Eligibility

Key inclusion criteria

• Singleton pregnancy
• Diagnosis of early onset preeclampsia as defined by the according to the SOMANZ guidelines
• Gestation between 24+0 and 33+ 6 weeks.
• Viable fetus, as determined by the treating obstetrician
• Able to safely continue pregnancy for 48 hours, or longer, as determined by the treating obstetrician
• Normal mid-trimester morphology scan, with no detectable significant anomalies.
• Deemed capable of understanding the information provided and able to give written informed consent (with interpreter use as required).
• >18 years of age

Minimum age

18 Years

Maximum age

No limit

Sex

Females

Can healthy volunteers participate?

Key exclusion criteria

• Eclampsia
• Current use of broccoli sprout extract supplement
• Contraindications to use (eg, intolerance of broccoli)
• Significant uncertainty in ensuring gestational age is within limits
• Unwillingness or inability to follow the procedures outlined in the PI and CF
• Mentally, cognitively or legally incapacitated or ineligible to provide informed consent
• Co-recruitment/participation in another clinical trial where there is a pharmaceutical or herbal or nutritional intervention (such trial interventions would also include: multi-vitamins, minerals, complementary and alternative medicines)
• Preexisting inflammatory bowel disease (Ulcerative Colitis and Crohn’s disease)

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Randomisation will be performed by a perinatal epidemiologist in our clinical unit who is not involved in the clinical trial. The randomisation sequence will then be provided to the pharmacist.

Prior to commencement of the trial, the broccoli sprout extract capsules or identical placebo capsules will be dispensed into bottles and sealed by the hospital clinical trials dedicated Pharmacist, who is not involved in the conduct of the trial. Thereafter, the bottles containing the trial capsules will be labelled as per the randomisation sequence. Ultimately, only the dedicated clinical trials pharmacist will have a record of each containers contents such that the participant, the researchers nor clinical staff attending the participant will know whether the participant has been administered broccoli sprout extract or placebo capsules.

Both Pharmacy and the third party involved in the randomisation process will retain the randomisation and associated dispensing information until all participants have completed the trial, all data entry and processing are complete and the database has been locked, at which point un-blinding will take place.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

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

All continuous measures will be assessed for normality of distribution and compared using non-parametric or parametric testing where appropriate. Continuous data will described using mean (SD) if normally distributed and median (IQR) when the distribution is skewed. Maternal and pregnancy characteristics will be analysed using t-test or Mann-Whitney U, to determine statistical difference between groups and to assess the randomisation. Primary and secondary analysis will be assessed with intention to treat analysis. The primary outcome measure of length to delivery will be presented as a mean time to delivery. A secondary time-to event analysis will be performed with adjustment for any significant differences between treatment groups. Data will be presented as hazard ratios and 95% Confidence intervals for difference between trial arms.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/06/2023

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

180

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [2]

Jessie McPherson Private Hospital - Clayton

Recruitment postcode(s) [1]

3168 - Clayton

Funding & Sponsors

Funding source category [1]

University

Name [1]

Monash University located at Monash Health

Address [1]

246 Clayton Road
Clayton
Victoria 3168

Country [1]

Australia

Primary sponsor type

Hospital

Name

Monash Health

Address

246 Clayton Road
Clayton
Victoria 3168

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health Ethics Comittee

Ethics committee address [1]

Monash Medical Centre
246 Clayton Road, 
Clayton, Victoria, 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/02/2018

Approval date [1]

20/09/2018

Ethics approval number [1]

Summary

Brief summary

Pre-eclampsia (PE) is a condition that occurs only in human pregnancy. The condition is a multi-system disorder and is typically recognised by the new onset of high blood pressure (‘hypertension’) after 20 weeks of pregnancy, which can also be accompanied by protein in the urine (‘proteinuria’). While the exact cause and mechanisms of PE have yet to be determined, we do know that the placenta (‘after birth’) plays an important part in development of the condition, and that once the baby has been born, and the placenta is then removed, a mother’s PE usually begins to get better.  Consequently, the only effective treatment for PE at this time is to deliver the baby and unfortunately, for many mothers with PE, this will mean that their baby will need to be born early in their pregnancies i.e. preterm, between 24-36 weeks. As a result, PE has the potential to be a significant cause of problems, for both mothers and their babies, in the immediate and long term.

Evidence derived from both the laboratory and also human studies, involving people who are not pregnant, has shown that sulforaphane, a compound that can be found naturally in broccoli sprouts, protects against cardiovascular disease and improves the health of blood vessels. For this reason, we believe that the administration of a broccoli sprout extract supplement containing sulforaphane, may offer a new ‘low risk, potential treatment for PE. Such a treatment would be highly beneficial to both the mother and her baby, since it could help doctors (obstetricians) to stabilize a mother’s PE and as a result, prolong the pregnancy. 

The aim of this project is to test whether a nutritional supplement containing broccoli sprout extract, which is high in sulforaphane, can prolong the time to delivery in pregnant women who have been diagnosed early onset preeclampsia.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof A/Prof Kirsten Palmer

Address

Department of Obstetrics and Gynaecology Monash University, Level 5 Monash Medical Centre, 246 Clayton Road, Clayton, Victoria, 3186,

Country

Australia

Phone

+61 3 9594 5145

Fax

kirsten.palmer@monash.edu

Contact person for public queries

Name

Sarah Marshall

Address

Monash University
Hudson Institute of Medical Research
27-31 Wright St
Clayton
Victoria 3168

Country

Australia

Phone

+61 3 9594 5145

Fax

sarah.marshall@monash.edu

Contact person for scientific queries

Name

Sarah Marshall

Address

The Ritchie Centre, Monash University, 27-31 Wright Street, Clayton, Victoria 3168

Country

Australia

Phone

+61 3 9594 5145

Fax

sarah.marshall@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Upon completion and publication of the trial results, de-identified trial data will be made available to others upon reasonable request.

When will data be available (start and end dates)?

We anticipate that the study will conclude in May 2025 and we hope to have the main data available shortly after the conclusion of the study. No end date is currently determined.

Available to whom?

1) The editors and peer reviewers of the final manuscript.
2) Interested parties who contact the senior author, requesting more information about the trial
3) Those individuals who read the journal where the manuscript has been accepted for publication are able to see the de-identified, aggregated data.

Available for what types of analyses?

Upon completion and publication of the trial results, de-identified trial data will be made available to others upon reasonable request. Associated documents such as protocol, PI&CF may be available by contacting the senior author. The senior author will determine who has access to documentation and data associated with this trial.

How or where can data be obtained?

Upon completion and publication of the trial results, de-identified trial data will be made available to others upon reasonable request. Such requests should be made to:
Professor Euan Wallace: euan.wallace@monash.edu

What supporting documents are/will be available?

Doc. No.	Type	Email
3847	Study protocol	euan.wallace@monash.edu
3848	Informed consent form	euan.wallace@monash.edu
3849	Statistical analysis plan	euan.wallace@monash.edu
3850	Ethical approval	euan.wallace@monash.edu

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Prolong: A double-blind randomised placebo-controlled trial of broccoli sprout extract in women with early onset preeclampsia. A clinical trial protocol.	2019	https://dx.doi.org/10.1136/bmjopen-2018-027493

N.B. These documents automatically identified may not have been verified by the study sponsor.

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