Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001238965
Ethics application status
Approved
Date submitted
3/09/2020
Date registered
18/11/2020
Date last updated
16/06/2024
Date data sharing statement initially provided
18/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Can a pre-conception weight loss program improve maternal and infant outcomes for women with overweight or obesity? A pragmatic randomised controlled trial (RCT).
Scientific title
Can a pre-conception weight loss program improve maternal and infant outcomes for women with overweight or obesity? A pragmatic randomised controlled trial (RCT).
Secondary ID [1] 302157 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PreBabe
Linked study record
The Pre-Babe Pilot study (ACTRN 12620000597998) has informed this trial.

Health condition
Health condition(s) or problem(s) studied:
Women with overweight (BMI greater than 25kg/m2 to less than 30kg/m2 ) 318803 0
Women with obesity BMI greater than 30kg/m2 319324 0
Condition category
Condition code
Diet and Nutrition 316816 316816 0 0
Obesity
Reproductive Health and Childbirth 316818 316818 0 0
Antenatal care
Reproductive Health and Childbirth 316819 316819 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this trial is to determine whether a meal replacement diet program (Impromy) in women (18-40 years) with overweight or obesity (BMI greater than 25 kg/m2) who are planning a pregnancy in the next 6 to 12 months improves perinatal outcomes and is cost-effective compared to usual care.

The intervention arm comprises an Australian meal replacement product (details available on the website https://cpc.impromy.com/) that will be delivered in 5 clinic /telehealth settings targeted for women planning pregnancy. All women will have a baseline (visit/consult 1), week 5 (visit/consult 2) and 10 week (visit/consult 3) appointment with a dietitian/midwife/researcher. The baseline and the 10 week appointments are 1 hour in duration and the 5 week appointment 30 minutes.

Women randomised to the intervention arm will be advised to follow the Impromy program for 10 weeks and will be registered with the PreBabe/Impromy website and given instructions on the meal replacement diet and provided with meal replacements. The Impromy program is based on alternate day energy restriction (e.g. Tuesday, Thursday, and Sunday comprise meal replacements and one healthy meal with protein and Monday, Wednesday, and Friday meal replacements plus salad/vegetables) to allow for one day per week to eat ad libitum ( e.g. Saturday).

A trained research dietitian or trained research officer/ midwife will deliver and monitor the dietary intervention. Individual estimated energy requirements will be calculated for all women at study visit 1 based on actual body weight, multiplied by appropriate physical activity levels and reduced by 25-30% to achieve energy restriction for weight loss. This individualised energy level determines the number of formulated meal replacements and the number of snacks for each woman. For example women with BMI 25 - 30 are likely to require 2 meal replacements per day and BMI > 30, 3 meal replacements per day. Meal replacements require reconstitution with 250 mL of either skim milk or a dairy-free alternative (unsweetened, calcium-enriched). The 10-week meal replacement diet program selected for this trial uses nutritionally complete meal replacement products. (Impromy meal replacements and supplied by Blackmores Ltd 20 Jubilee Avenue Warriewood 2102., Australia; MR =~1000kJ, 25g protein, 4g fat, 27g carbohydrate, 6g fibre with each containing 25% recommended daily intake for Vitamin A, Thiamin, Riboflavin, Niacin, Folate, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Calcium, Iodine, Iron, Magnesium, Phosphorus and Zinc.)

The total daily macronutrient distribution for the MRP diet shown above was 31% of total energy as carbohydrate, 38% protein and 28% total fat (52% monounsaturated fat and 17% polyunsaturated fat) with the remaining 3% non-soluble fibre. Prescribed snack option for the plan include: fruit, low fat dairy, whole-grains and nut/seed/legume. The number of snacks allocated per day is also tailored to individual energy requirements for weight loss.

Behavioural strategies included in the dietitian/research midwife visits and the accompanying website include, goal setting, self-monitoring of behaviour and progress, stimulus control (e.g. recognising triggers that prompt unplanned eating), cognitive restructuring (modifying unhelpful thoughts), problem solving, assertiveness, slowing the rate of eating, reinforcing changes and relapse prevention. We will also provide a helpline for the program so women are able to access a dietitian for advice during the 10 weeks. This support will be available via a dedicated email monitored by 3 study team members and a study mobile phone during business hours. The website provides general advice regarding the program and weight loss support plus a virtual consultation which has been informed through the FAQs of the CSIRO pilot trial and has been designed by dietitians Women will also receive a copy of the printed booklet from the Australian Government website regarding healthy weight. http://healthyweight.health.gov.au

We will monitor adherence to the meal replacements by questionnaires, weight measurement at the study visit and a count of supplied products to the participating women.
Intervention code [1] 318456 0
Prevention
Intervention code [2] 318781 0
Behaviour
Intervention code [3] 318782 0
Lifestyle
Comparator / control treatment
Recommended weight loss advice delivered in a clinical setting. There will be three clinic visits/telehealth consults at baseline (visit 1),week 5 (visit 2) and week 10 (visit 3). Visits 1 and 3 will be approximately 1 hour in duration with a dietitian/ research mid-wife and blood samples collected and visit 2 will be 30 minutes in duration with a dietitian/research mid-wife, If the consults are completed via telehealth the pathology tests are completed at a pathology lab close to where the participant lives.

Participants allocated to control arm will be advised on the Australian dietary guidelines for healthy eating and receive advice as per existing RANZCOG and Preventative Activities for General Practice professional college guidelines. They will receive a brochure on the healthy weight guide http://healthyweight.health.gov.au and be informed about the NSW Get Healthy Program and a direct referral completed if desired https://www.gethealthynsw.com.au/ . A similar service will be accessed for women in Victoria.
Control group
Active

Outcomes
Primary outcome [1] 324929 0
Composite perinatal outcome including one or more of the following maternal and infant outcomes: 1. Maternal outcomes (gestational diabetes mellitus; pre-eclampsia; first Caesarean section) 2. Infant outcomes (perinatal death; LGA (birth weight >90th centile); admission to a neonatal unit).
Timepoint [1] 324929 0
Assessed within 1 month after birth by access to electronic medical record and perinatal data
Secondary outcome [1] 386241 0
Stillbirth (infant loss > 20 weeks of gestation)
Timepoint [1] 386241 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [2] 386249 0
neonatal death
Timepoint [2] 386249 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [3] 386250 0
Need for resuscitation at delivery
Timepoint [3] 386250 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [4] 386251 0
Infant shoulder dystocia
Timepoint [4] 386251 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [5] 386252 0
Infant nerve palsy as a result of the birth.
Timepoint [5] 386252 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [6] 386253 0
Any infant fracture due to delivery.
Timepoint [6] 386253 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [7] 386254 0
Birthweight
Timepoint [7] 386254 0
Assessed at birth using digital scales as per normal clinical practice
Secondary outcome [8] 386255 0
Breastfeeding at discharge
Timepoint [8] 386255 0
Assessed before discharge and through medical record
Secondary outcome [9] 386256 0
Gestational hypertension
Timepoint [9] 386256 0
Assessed at birth by linkage to pregnancy medical record
Secondary outcome [10] 386257 0
Assisted vaginal birth
Timepoint [10] 386257 0
Type of delivery assessed at birth through medical record (routine perinatal data collection)
Secondary outcome [11] 386258 0
Spontaneous vaginal birth
Timepoint [11] 386258 0
Type of delivery assessed at birth through medical record (routine perinatal data collection)
Secondary outcome [12] 386259 0
Post-partum hemorrhage
Timepoint [12] 386259 0
Assessed within 1 month after birth through routine perinatal data collection and access to medical record
Secondary outcome [13] 386260 0
Composite outcome of maternal 3rd and 4th degree tears. A third degree tear is a tear or laceration through the perineal muscles and the muscle layer that surrounds the anal canal. A fourth degree tear goes through the anal sphincter all the way to the anal canal or rectum.
Timepoint [13] 386260 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [14] 386261 0
Length of stay in hospital
Timepoint [14] 386261 0
Assessed at discharge through routine perinatal data collection and access to medical record
Secondary outcome [15] 386262 0
Incremental cost-effectiveness analysis will determine whether the intervention represents ‘value-for-money’ measured against usual care.

The cost of delivering the weight loss intervention will be determined using standard methods and quality of life assessed using SF36 at baseline and 10 weeks. Health care utilisation during pregnancy and birth will be determined through data linkage to: Medicare Benefits Schedule and Pharmaceutical Benefits Scheme datasets, Admitted Patient and Perinatal Data Collection. Hospital costs will be derived from Australian Refined Diagnosis Related Groups (AR-DRG) cost weights based on the type of delivery, length of stay and the level of complications/co-morbidities. We will calculate incremental cost per composite outcome avoided and incremental cost/QALY in the intervention compared with usual care. Bootstrapping will be used to estimate a distribution around costs and health outcomes, and to calculate the confidence intervals around the incremental cost-effectiveness ratios. One-way and multi-way sensitivity analysis will be conducted around key variables. We will derive a cost-effectiveness acceptability curve based on willingness to pay thresholds.
Timepoint [15] 386262 0
At trial completion
Secondary outcome [16] 386263 0
Composite maternal and childhood outcomes in the first 2000 days (from conception to birth to infant growth) as assessed by maternal and infant medical records.
Timepoint [16] 386263 0
Assessed yearly for 5 years through maternal consent for linkage of the perinatal data to later health outcomes including childhood hospitalisation, education outcomes and subsequent pregnancies.
Secondary outcome [17] 386567 0
Gestational Diabetes Mellitus
Timepoint [17] 386567 0
Assessed within 1 month after birth by access to electronic medical record and perinatal data
Secondary outcome [18] 386568 0
Pre-eclampsia
Timepoint [18] 386568 0
Assessed within 1 month after birth by access to electronic medical record and perinatal data
Secondary outcome [19] 386569 0
Caesarean section
Timepoint [19] 386569 0
Assessed at birth through routine perinatal data collection and access to medical record
Secondary outcome [20] 386570 0
Large for gestational age (LGA) that is their birthweight is above the 90th percentile for their gestational age and sex, as determined by national percentiles.
Timepoint [20] 386570 0
Assessed within 1 week after birth as plotted on a population based percentile chart from birthweight and documented in electronic medical records.
Secondary outcome [21] 388691 0
Quality of life using SF36 validated questionnaire
Timepoint [21] 388691 0
Baseline, 10 weeks (completion of weight loss program) and 12 months post intervention
Secondary outcome [22] 388692 0
Gestational Weight Gain (calculated using change in prepregnancy weight to end of pregnancy)
Timepoint [22] 388692 0
Pre-pregnancy weight, weight at end of trimester 1, 2 and 3 (or just prior to birth)
Secondary outcome [23] 388693 0
Admission to neonatal unit
Timepoint [23] 388693 0
Assessed after birth using routinely collected data
Secondary outcome [24] 388696 0
Reason for admission to neonatal unit
Timepoint [24] 388696 0
Collected using routinely collected admission data
Secondary outcome [25] 388697 0
Time to conception
Timepoint [25] 388697 0
Assessed monthly over first 12 months and 6 monthly 12-24 months via combination of SMS/Email
Secondary outcome [26] 388700 0
Apgar Scores
Timepoint [26] 388700 0
Assessed at birth and collected through routine data collection

Eligibility
Key inclusion criteria
– Women with a BMI greater than or equal to 25kg/m2
- Planning a pregnancy within 6 to 12 months
– Willing to attend 3 consults either in the clinic or via telehealth
- Provide pregnancy and birth details to the research team
– Willing to follow a weight loss dietary protocol for 10 weeks
– Has been weight stable (i.e. less than 3 kg weight loss) for the past 2 months.
Minimum age
18 Years
Maximum age
40 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
– Significant pre-existing, diagnosed medical condition that may prevent them from participating in the study, including but not limited to: Kidney disease or renal impairment; Gall bladder disorders or stones; Liver disease (e.g. cirrhosis); severe cardiovascular disease where rapid weight loss is contraindicated eg Cardiac arrhythmia, congenital heart disease; Malabsorptive Gastrointestinal disease (including celiac, Crohns disease);
– History of bariatric surgery;
– Severe depression;
– Cancer (unless benign or non-progressive skin cancer);
– Type 1 diabetes and type 2 diabetes if on insulin.
– Regular use of medications prescribed by a medical practitioner that are deemed unsuitable for this trial – as determined by the appointed study physician during screening process;
– A food allergy/intolerance to, or not willing to consume, the foods prescribed in the protocol;
- Postpartum <6 months or currently breastfeeding;
– A person considered by the investigator to be unwilling, unlikely or unable to comprehend or comply with the study protocol;
- A person unable to to provide informed consent

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)
The randomization sequence will be generated centrally using computer randomisation in variable block permutation . It will be uploaded in REDCap independent to the study team and then locked. Women will be consented prior to randomization.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation will be centrally computer generated. Block randomisation will be used with a 1:1 allocation ratio to the meal replacement diet program or usual care and will be stratified by age (less than and equal to 35 years), previous caesarean section and BMI (25.0 to less than 30.0 kg/m2 versus greater than and equal to 30.0 kg/m2).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Treatment allocation will be centrally performed at the NHMRC Clinical Trials Centre. Block randomisation will be used with a 1:1 allocation ratio to the meal replacement diet program or usual care and will be stratified by age (less than and equal to 35 years), previous caesarean section and BMI (25.0 to less than 30.0 kg/m2 versus greater than and equal to 30kg/m2).
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analyses will be based on intention to treat. The primary analysis will assess the effect of the intervention on the presence of the primary composite perinatal outcome at 12 months by directly calculating relative risks and their 95% confidence interval. Relative risks will be calculated using log binomial regression. Secondary analyses will assess the effect of the intervention on the secondary outcomes. If the secondary outcomes are binary, relative risks will be calculated as above. Continuous secondary outcomes will be analysed by means of analysis of variance if they are normally distributed and by means of nonparametric tests if their distribution is not normal. Adjustments will be made to account for clustering of babies with the same mothers if there is evidence of increased variance owing to the number of twins in the study. A step-down Sidak adjustment [1] will be made for analyses involving multiple primary clinical end points to assess if the results remain consistent. A p-value of 0.05 will indicate statistical significance; all p-values will be two-sided. The Benjamini-Hochberg-Simes critical p value will be used to account for secondary analyses, controlling for a 5% false discovery rate [2] A protocol and statistical analysis plan will be published in an open access journal before data analysis.

1. Hochberg, Y. and A.C. Tamhane, Multiple comparison procedures. 1987: John Wiley & Sons, Inc.
2. Benjamini, Y., Hochberg, Y., Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society. Series B (Methodological),, 1995. 57(1): p. 289-300.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/01/2021
Actual
8/12/2021
Date of last participant enrolment
Anticipated
8/04/2025
Actual
Date of last data collection
Anticipated
30/06/2029
Actual
Sample size
Target
1927
Accrual to date
295
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17345 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 17346 0
Westmead Hospital - Westmead
Recruitment hospital [3] 17347 0
Royal Hospital for Women - Randwick
Recruitment hospital [4] 17348 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 17349 0
Nepean Hospital - Kingswood
Recruitment hospital [6] 22201 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 31073 0
2050 - Camperdown
Recruitment postcode(s) [2] 31074 0
2145 - Westmead
Recruitment postcode(s) [3] 31075 0
2031 - Randwick
Recruitment postcode(s) [4] 31076 0
2065 - St Leonards
Recruitment postcode(s) [5] 31077 0
2747 - Kingswood
Recruitment postcode(s) [6] 37358 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 306584 0
Government body
Name [1] 306584 0
Dept of Health Australian Federal Government
Country [1] 306584 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
The University of Sydney
Level 3 F23 Administration Building
The University of Sydney 2006
NSW
Country
Australia
Secondary sponsor category [1] 307114 0
None
Name [1] 307114 0
Address [1] 307114 0
Country [1] 307114 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306767 0
Research Ethics & Governance Office | Royal Prince Alfred Hospital
Ethics committee address [1] 306767 0
Ethics committee country [1] 306767 0
Australia
Date submitted for ethics approval [1] 306767 0
28/09/2020
Approval date [1] 306767 0
18/12/2020
Ethics approval number [1] 306767 0
X20-0439/2020/ETH02421

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

Contacts
Principal investigator
Name 104954 0
Prof Adrienne Gordon
Address 104954 0
University of Sydney, Charles Perkins Centre Research and Education Hub D17 The University of Sydney | NSW | 2006
Country 104954 0
Australia
Phone 104954 0
+61405816782
Fax 104954 0
Email 104954 0
adrienne.gordon@sydney.edu.au
Contact person for public queries
Name 104955 0
Dr Roslyn Muirhead
Address 104955 0
University of Sydney, Charles Perkins Centre Research and Education Hub D17 The University of Sydney | NSW | 2006
Country 104955 0
Australia
Phone 104955 0
+61 413204450
Fax 104955 0
Email 104955 0
roslyn.muirhead@sydney.edu.au
Contact person for scientific queries
Name 104956 0
Adrienne Gordon
Address 104956 0
University of Sydney, Charles Perkins Centre Research and Education Hub D17 The University of Sydney | NSW | 2006
Country 104956 0
Australia
Phone 104956 0
+61405816782
Fax 104956 0
Email 104956 0
adrienne.gordon@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Demographic and outcome data
When will data be available (start and end dates)?
The data will be available after publication by contacting the research team who will discuss with prebabe steering committee. There is no end date specified.
Available to whom?
Following request to study team for ethically approved projects requesting data available within the pre-babe trial and documented in the published protocol (to be submitted )
Available for what types of analyses?
Systematic review
IPD
Prospective meta-analysis
How or where can data be obtained?
By contacting study team - study specific email is cpc.prebabe.study@sydney.edu.au, principal investigator contact details adrienne.gordon@sydney.edu.au - telephone 02 9515 8248


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.