ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12613001142729

Ethics application status

Approved

Date submitted

27/09/2013

Date registered

14/10/2013

Date last updated

28/06/2023

Date data sharing statement initially provided

28/06/2023

Date results provided

28/06/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Omega-3 fats to reduce the incidence of prematurity: the ORIP trial

Scientific title

Omega-3 fats to reduce the incidence of prematurity in healthy women with a singleton or multiple pregnancy less than 20 weeks gestation

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

The ORIP trial

Linked study record

Health condition

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

Early preterm birth

Condition category

Condition code

Diet and Nutrition

Other diet and nutrition disorders

Reproductive Health and Childbirth

Fetal medicine and complications of pregnancy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

3 capsules of fish oil containing a total dose of approximately 800 mg of DHA will be administered orally per day until 34 weeks gestation or birth (whichever occurs first). Women will be asked to return unused supplements at the end of the 34 weeks gestation when a spot blood sample is taken. The proportion of capsules returned will serve as a measure of adherence. DHA concentration at the end of intervention will be used as an independent biomarker of adherence.

Intervention code [1]

Prevention

Comparator / control treatment

Vegetable oils with a trace of DHA to aid masking

Control group

Placebo

Outcomes

Primary outcome [1]

Evaluate the impact of fish oil supplementation on the incidence of early preterm birth compared with placebo.

Timepoint [1]

Early preterm birth defined as delivery before 34 weeks completed gestation age.

Secondary outcome [1]

Incidence of post-term induction or post-term pre labour caesarean delivery via case note audit based on LMP and U/S report

Timepoint [1]

at birth

Secondary outcome [2]

Preterm birth (GA <37 completed weeks at birth) via case note audit based on LMP and U/S report

Timepoint [2]

at birth

Secondary outcome [3]

The safety and tolerability of DHA supplementation.
Tolerability: By structured interview, post-term induction/post-term pre-labour Csection:
medical case note audit based on LMP and U/S

Timepoint [3]

Ongoing throughout the study.

Secondary outcome [4]

Low Birth Weight (LBW): birth wt <2500g

Timepoint [4]

at birth

Secondary outcome [5]

Small for gestational age: birth wt < 10 centile for corresponding GA and sex.

Timepoint [5]

at birth

Secondary outcome [6]

Neonatal complications will be assessed via case note audit. The following complications will be recorded:
1. Jaundice required phototherapy
2. Hypoglycaemia required intravenous dextrose infusion
3. Neonatal convulsion
4. Brain injury
5. Surgery
6. Necrotising Enterocolitis (NEC)
7. Sepsis
8. Retinopathy of prematurity (ROP)
9. Other

Timepoint [6]

up to 28 days post birth

Secondary outcome [7]

Admission to neonatal intensive care unit via case note audit

Timepoint [7]

up to 28 days post birth

Eligibility

Key inclusion criteria

A singleton or multiple pregnancy and less than 20 weeks gestation.

Able to give informed consent.

Minimum age

No limit

Maximum age

No limit

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Women with a known fetal abnormality will be excluded.

Women who are taking dietary supplements containing LCPUFA > 150mg/day.

Women who are taking dietary supplements containing LCPUFA < / = 150mg/day and are not willing to stop.

Women with bleeding disorders where fish oil is contraindicated or are on anticoagulant therapy.

Women with a history of drug or alcohol abuse.

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)

Women will be approached to enter the trial by research staff at the time of attending the hospital for their first antenatal booking visit. If they are interested in the study, they will be screened and have the study explained to them. When all the inclusion and exclusion criteria have been checked and the eligibility of the women confirmed, a copy of the information sheet and consent form will be given to the women.

The information sheet will describe the prurpose of the study, the procedures to be followed, and the risks and benefits of participation. The research staff will conduct the informed consent discussion and will check that information provided is understood and answer any questions about the study. Consent will be voluntary and free from coercion.

Upon receiving written informed consent, a research staff member will collect baseline data including contact details, birth order, age, weight, height, heighest level of education, occupation, smoking status and pregnancy related background data. A blood sample will also be collected to assess fatty acid status. Women will then be randomly assigned to treatment or control group. A copy of the information sheet and signed consent form will be provided to the women and the original filed in the case report form (CRF).

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

Women will be assigned to study packs labelled with a unique study number assigned through a web-based randomisation service. Allocation will follow a computer generated randomisation schedule with balanced variable blocks, prepared by an independent consultant. Stratification will be by centre and supplements used prior to trial entry (containing no LCPUFA vs. less than or equal to 150mg LCPUFA/day).

Each study pack will contain either treatment or control capsules, pre-packed according to the randomisation schedule. Participants and their family, care providers, outcome assessors and data analysts will be blinded to randomisation group.

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 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

All analyses will be performed on an intention-to-treat basis. The primary outcome of early preterm birth will be compared between treatment and control groups using log binomial regression. Adjustment will be made for the stratification variables centre and supplements, as well as pre-specified prognostic baseline variables. Results will be presented as a relative risk with confidence interval and 2-sided p-value. Statistical significance will be assessed accounting for the pre-specified interim analysis using the O'Brien-Fleming approach. All analyses will follow a pre-specified statistical analysis plan. Infant outcomes will be analysed using generalised estimating equations to account for clustering due to multiple births.

Missing data (deaths) will be multiple imputed. Sensitivity analyses will also be performed using the original unimputed data, excluding deaths.

The sample size estimation was based on our published DOMInO trial (Makrdies et al, JAMA, 2010; 304: p 1675-83) of women with singleton pregnancies, treatment resulted in a 1.16% absolute reduction (from 2.25% to 1.09%) in the incidence of early preterm birth (EPTB). Inclusion of women with multiple pregnancies in the ORIP trial is expected to result in a small increase in the incidence of EPTB in both treatment groups, since EPTB is more common in multiple pregnancies. To demonstrate an absolute reduction in the incidence of EPTB of 1.16% (from 2.45% to 1.29%) with 85% power and overall two-sided alpha=0.05, a sample size of 2618 per group (i.e. 5236 total) is required. Allowing for a loss to follow up of 5%, a total of 5540 women is required to ensure adequate power for the primary outcome. Since EPTB is a mother level outcome, the sample size calculations define the number of mothers that need to be recruited and no adjustment for clustering due to multiple pregnancies is required for this outcome.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

21/10/2013

Actual

1/11/2013

Date of last participant enrolment

Anticipated

31/12/2017

Actual

28/04/2017

Date of last data collection

Anticipated

24/11/2017

Actual

29/12/2017

Sample size

Target

5540

Accrual to date

Final

5544

Recruitment in Australia

Recruitment state(s)

QLD,SA,WA,VIC

Recruitment hospital [1]

Womens and Childrens Hospital - North Adelaide

Recruitment hospital [2]

Flinders Medical Centre - Bedford Park

Recruitment hospital [3]

Werribee Mercy Hospital - Werribee

Recruitment hospital [4]

Mater Mother's Hospital - South Brisbane

Recruitment hospital [5]

Lyell McEwin Hospital - Elizabeth Vale

Recruitment hospital [6]

Joondalup Health Campus - Joondalup

Recruitment postcode(s) [1]

5006 - North Adelaide

Recruitment postcode(s) [2]

5042 - Bedford Park

Recruitment postcode(s) [3]

3030 - Werribee

Recruitment postcode(s) [4]

5112 - Elizabeth Vale

Recruitment postcode(s) [5]

4101 - South Brisbane

Recruitment postcode(s) [6]

6027 - Joondalup

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

South Australian Health and Medical Research Institute

Address

North Adelaide, SA 5000

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Women's and Children's Health Network Human Research Ethics Committee

Ethics committee address [1]

Level 2 Samuel Way Building
72 King William Rd
North Adelaide SA 5006

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/01/2013

Approval date [1]

01/05/2013

Ethics approval number [1]

HREC/13/WCHN/10

Summary

Brief summary

Early preterm birth (EPTB) is the major cause of perinatal mortality, serious neonatal morbidity and moderate to severe childhood disability in developed countries.  Currently, effective broadly applicable primary prevention strategies to reduce the risk of EPTB in the general population are lacking. This randomised controlled trial will determine whether n-3 LCPUFA supplementation from mid-pregnancy (before 20 weeks gestation) to 34 weeks gestation reduces the risk of EPTB. The study is a double blind, randomised controlled multi-centre trial. The primary outcome is the Incidence of early preterm birth (EPTB) defined as delivery before 34 completed weeks gestation. Secondary outcomes include  Incidence of post-term induction or post-term pre-labour caesarean section, other outcomes known to be directly affected by EPTB, and the safety and tolerability of DHA supplementation. Eligible women will be randomly allocated to either intervention (~800 mg DHA) or control groups..  Women will receive intervention from trial entry (<20 weeks) to 34 weeks gestation or birth, whichever comes first. Women will be followed up to discharge after birth.   The study will be conducted over a 5 year period 2013 to 2017.  A total of 5540 pregnant women will be recruited to take part in the trial.

Trial website

Trial related presentations / publications

Zhou SJ, Best K, Gibson R, et al. Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial. BMJ Open 2017;7:e018360. doi:10.1136/ bmjopen-2017-018360 

Makrides M, Best K, Yelland L, McPhee A, Zhou S, Quinlivan J, Dodd J, Atkinson E, Safa H, van Dam J, Khot N, Dekker G, Skubisz M, Anderson A, Kean B, Bowman A, McCallum C, Cashman K, Gibson R. A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery. N Engl J Med. 2019 Sep 12;381(11):1035-1045. doi: 10.1056/NEJMoa1816832. PMID: 31509674.

Best KP, Gibson RA, Yelland LN, Leemaqz S, Gomersall J, Liu G, Makrides M. Effect of omega-3 lcpufa supplementation on maternal fatty acid and oxylipin concentrations during pregnancy. Prostaglandins Leukot Essent Fatty Acids. 2020 Nov;162:102181. doi: 10.1016/j.plefa.2020.102181. Epub 2020 Sep 28. PMID: 33038832.

Simmonds LA, Sullivan TR, Skubisz M, Middleton PF, Best KP, Yelland LN, Quinlivan J, Zhou SJ, Liu G, McPhee AJ, Gibson RA, Makrides M. Omega-3 fatty acid supplementation in pregnancy-baseline omega-3 status and early preterm birth: exploratory analysis of a randomised controlled trial. BJOG. 2020 Jul;127(8):975-981. doi: 10.1111/1471-0528.16168. Epub 2020 Mar 3. PMID: 32034969.

Public notes

Attachments [1]

/AnzctrAttachments/363566-Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth_the ORIP trial.pdf (Protocol)

Contacts

Principal investigator

Name

Dr Shao (Jo) Zhou

Address

FOODplus Research Centre
The University of Adelaide, Waite Campus
PMB 1
Glen Osmond SA 5064

Country

Australia

Phone

+61 8 8313 2065

Fax

+61 8 8303 7135

jo.zhou@adelaide.edu.au

Contact person for public queries

Name

Karen Best

Address

SAHMRI, North Terrace, Adelaide SA 5000 Australia

Country

Australia

Phone

+61 8 8128 4404

Fax

+61 8 8239 0267

karen.best@sahmri.com

Contact person for scientific queries

Name

Maria Makrides

Address

SAHMRI, North Terrace, Adelaide SA 5000 Australia

Country

Australia

Phone

+618 8128 4416

Fax

+61 8 8303 7135

maria.makrides@sahmri.com

Data sharing statement

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

Yes

What data in particular will be shared?

Yes. De-identified, individual participant data (IPD) that underlie the results reported in the primary paper (text, tables, figures and appendices) will be available. Dataset(s) will be limited to those participants and variables that are necessary for completion of the approved research proposal.

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

Data requests will be accepted beginning 3 months and ending 5 years after publication of trial results.

Available to whom?

Data will be available to researchers who provide a methodologically sound research proposal following review and approval by the trial steering committee and completion of a signed data
access agreement.

Available for what types of analyses?

Data may be shared with researchers who provide a methodologically sound research proposal following review and approval by the trial steering committee and completion of a signed data access agreement.

How or where can data be obtained?

All data requests should be made to maria.makrides@sahmri.com or karen.best@sahmri.com

What supporting documents are/will be available?

Doc. No.	Type	Email	Other Details
19556	Study protocol
19557	Statistical analysis plan	maria.makrides@sahmri.com
19558	Other	maria.makrides@sahmri.com	Case Report Form

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	A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery.	2019	https://dx.doi.org/10.1056/NEJMoa1816832
Embase	Predictors of compliance with higher dose omega-3 fatty acid supplementation during pregnancy and implications for the risk of prematurity: exploratory analysis of the ORIP randomised trial.	2023	https://dx.doi.org/10.1136/bmjopen-2023-076507

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

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically