Membrane Sweeping to Prevent Post-term Pregnancy: The MILO Study (MILO)

May 12, 2020 updated by: Prof. Declan Devane, National University of Ireland, Galway, Ireland

Feasibility Study Protocol of a Pragmatic, Randomised Controlled Pilot Trial: Membrane Sweeping to Prevent Post-term Pregnancy: The MILO Study

Multicentre, pragmatic, parallel group, pilot randomised controlled trial with an embedded factorial design.

Study Overview

Detailed Description

The primary aim of the MILO study is to inform the optimal design of a future definitive randomised trial to evaluate the effectiveness (including optimal timing and frequency) of membrane sweeping to prevent post-term pregnancy. We will also assess the acceptability and feasibility of the proposed trial interventions to clinicians and women (through focus group interviews).

Methods/Design

Multicentre, pragmatic, parallel group, pilot randomised controlled trial with an embedded factorial design. Pregnant women with a live, singleton fetus ≥ 38 weeks gestation, cephalic presentation, longitudinal lie, intact membranes, English speaking and ≥18 years of age will be randomised in a 2:1 ratio to:

• Membrane sweep versus no membrane sweep

Women allocated randomly to a sweep will then be randomised further (factorial component) to:

  • early (from 39 weeks) versus late (from 40 weeks) sweep commencement; and
  • a single verses weekly sweep

The proposed feasibility study consists of four work packages i.e., (1) a multicentre, pilot randomised trial, 2) a health economic analysis and 3) a qualitative study (4) a study within the host trial (a SWAT).

Study Type

Interventional

Enrollment (Anticipated)

132

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Pregnant women carrying a live singleton fetus ≥ 38 weeks completed gestation.
  • (Gestational age will be calculated from the first day of the last menstrual period and an
  • ultrasound examination carried out in the 2nd trimester)
  • Longitudinal lie
  • Cephalic presentation
  • Intact amniotic
  • ≥ 18 years of age on enrollment

Exclusion Criteria:

  • Not able to communicate in english
  • contraindications to a vaginal examination
  • contraindications to a vaginal birth

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Group A
Membrane sweep @ 39 weeks' gestation only
Amniotic membrane sweeping is defined as the manual detachment of the inferior pole of the amniotic membranes from the lower uterine segment. This is performed with consent by a clinician digitally through a circular motion during a vaginal examination. If the cervical os is closed massage of the cervix will be accepted.
EXPERIMENTAL: Group B
Membrane sweep @ 40 weeks' gestation only
Amniotic membrane sweeping is defined as the manual detachment of the inferior pole of the amniotic membranes from the lower uterine segment. This is performed with consent by a clinician digitally through a circular motion during a vaginal examination. If the cervical os is closed massage of the cervix will be accepted.
EXPERIMENTAL: Group C
Membrane sweep @ 39, 40 and 41 weeks' gestation or until onset of labour
Amniotic membrane sweeping is defined as the manual detachment of the inferior pole of the amniotic membranes from the lower uterine segment. This is performed with consent by a clinician digitally through a circular motion during a vaginal examination. If the cervical os is closed massage of the cervix will be accepted.
EXPERIMENTAL: Group D
Membrane sweep @ 40 and 41 weeks' gestation or until onset of labour
Amniotic membrane sweeping is defined as the manual detachment of the inferior pole of the amniotic membranes from the lower uterine segment. This is performed with consent by a clinician digitally through a circular motion during a vaginal examination. If the cervical os is closed massage of the cervix will be accepted.
NO_INTERVENTION: Control Group
Women in the control arm will not receive a membrane sweep and will receive usual care (as defined by local hospital protocols and vaginal examination to determine Bishop score only).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment
Time Frame: Duration of the recruitment process (approximately 8 months )
Evaluation of the number and percentage of eligible women who are recruited and randomised to the study. Assessed by study-specific checklists.
Duration of the recruitment process (approximately 8 months )
Retention
Time Frame: At month 15 approximately
Evaluation of the number and percentage of eligible women who are randomised, take part in and adhere to the study protocols. Data will be extracted from routinely collected data.
At month 15 approximately
Adherence with the trial interventions.
Time Frame: At month 15 approximately
Evaluation of adherence with the trial interventions, and reasons for non-compliance assessed by study-specific checklists. Data will be extracted from routinely collected data and focus group interviews with clinicians and participants at six weeks post intervention.
At month 15 approximately
Evaluation of the randomisation process.
Time Frame: At month 15 approximately
Evaluation of effective allocation of participants to the intervention/control group assessed by study-specific checklists and evaluation of the randomisation protocol throughout the randomisation period.
At month 15 approximately
Evaluation of attrition rates
Time Frame: At month 15 approximately
Evaluation of attrition rates assessed by study-specific checklists. Data will be extracted from routinely collected data.
At month 15 approximately
Evaluation of the types of attrition
Time Frame: At month 21 approximately
Evaluation of the types of attrition assessed by case report forms. Data will be extracted from routinely collected data.
At month 21 approximately
Evaluation of the data collection process through study specific checklists
Time Frame: At month 21 approximately
Evaluated, statistically and narratively, by assessing the completeness of outcome measurements at baseline and postnatal (6 weeks) through study specific checklists. Researchers will manually examine the data collected. They will assess the proportion of complete data collection forms, the quality of data collected and the applicability of this data in facilitating pilot trial outcomes.
At month 21 approximately
Estimate the main effect of individual intervention components and their interactions
Time Frame: At month 21 approximately
Estimates (with measures of uncertainty) of the main effect of individual intervention components and any interaction effect between the main effects of the embedded factorial design will be assessed and reported using regression analysis.
At month 21 approximately
Evaluation of the data analysis process
Time Frame: At month 21 approximately
As this is a feasibility study formal hypothesis testing will not be undertaken. Researchers will manually examine the data collected. Evaluation of the data analysis process will be undertaken through the assessment of gaps and limitations to the analysis process measured by study-specific checklist. Findings will be reported through descriptive statistics and graphical summaries.
At month 21 approximately
Evaluation of the EQ5D
Time Frame: At month 21 approximately
Assessment of the mechanism of, timing of and delivery of the EQ5D through study specific checklists.
At month 21 approximately
Feasibility of cost analyses process through analysis of study specific documentation.
Time Frame: At month 21 approximately
Assessment of data collection tools to undertake cost effectiveness analysis through study specific documentation. Researchers will manually examine data to assess the mechanism of, timing of and delivery of the cost analysis tools.
At month 21 approximately
Feasibility of the cost effectiveness analyses
Time Frame: At month 21 approximately
Assessment of the mechanism and utilisation of the incremental cost-effectiveness ratio (ICER), through study specific checklists.
At month 21 approximately

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants achieving a spontaneous onset of labour
Time Frame: From time of randomisation to commencement of spontaneous onset of labour or formal induction of labour or caesarean section (up to 5 weeks)
Labour which begins spontaneously.
From time of randomisation to commencement of spontaneous onset of labour or formal induction of labour or caesarean section (up to 5 weeks)
Number of participants who underwent an induction of labour
Time Frame: From time of randomisation to commencement of formal induction of labour (up to 5 weeks).
Formal induction of labour using pharmacological or surgical methods.
From time of randomisation to commencement of formal induction of labour (up to 5 weeks).
Number of participants achieving a spontaneous vaginal birth
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
Spontaneous vaginal birth
From time of randomisation to birth of baby (up to 5 weeks)
Instrumental birth
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
Vaginal birth which is assisted with the use of instruments.
From time of randomisation to birth of baby (up to 5 weeks)
Caesarean Section
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
Birth which is achieved through the surgical procedure caesarean section.
From time of randomisation to birth of baby (up to 5 weeks)
Post-Partum Haemorrhage ≥ 500mls
Time Frame: From time of birth to 24 hours after the birth of baby.
Blood loss ≥ 500mls within the first 24 hours of the birth of a baby
From time of birth to 24 hours after the birth of baby.
Antepartum haemorrhage requiring hospital admission
Time Frame: From 24+0 weeks of pregnancy to birth of baby (up to 18 weeks)
Bleeding from the genital tract, from 24+0 weeks of pregnancy and before the birth of the baby.
From 24+0 weeks of pregnancy to birth of baby (up to 18 weeks)
Uterine hyperstimulation with/without fetal heart rate (FHR) changes
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
Uterine hyperstimulation defined as uterine tachysystole (more than five contractions per ten minutes for at least twenty minutes) and uterine hypersystole/hypertonicity (a contraction lasting at least two minutes). These may or not be associated with changes in the fetal heart rate pattern (persistent decelerations, tachycardia or decreased short term variability.
From time of randomisation to birth of baby (up to 5 weeks)
Serious maternal death or morbidity
Time Frame: From time of randomisation to six weeks postnatal (up to 11 weeks).
Serious maternal death or morbidity (e.g. uterine rupture, admission to intensive care unit, septicaemia)
From time of randomisation to six weeks postnatal (up to 11 weeks).
Epidural analgesia
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
Introduction of a local anaesthetic into the epidural space of the vertebral canal.
From time of randomisation to birth of baby (up to 5 weeks)
Augmentation of labour
Time Frame: From commencement of established labour to birth of baby (up to 2 days)
The stimulation of uterine contractions using pharmacologic methods or artificial rupture of membranes to increase their frequency and/or strength following the onset of spontaneous labor or contractions following spontaneous rupture of membranes (ACOG 2014)
From commencement of established labour to birth of baby (up to 2 days)
Pyrexia in labour
Time Frame: From commencement of established labour to birth of baby (up to 2 days)
Pyrexia that developed anytime after onset of labour.
From commencement of established labour to birth of baby (up to 2 days)
Uterine rupture
Time Frame: From time of randomisation to birth of baby (up to 5 weeks)
All clinically significant ruptures of unscarred or scarred uteri. Trivial scar dehiscence noted incidentally at the time of surgery will be excluded
From time of randomisation to birth of baby (up to 5 weeks)
EQ5D-5L
Time Frame: From time of randomisation to six weeks postnatal (up to 11 weeks)
EuroQol EQ5D-5L survey instrument.
From time of randomisation to six weeks postnatal (up to 11 weeks)
Serious neonatal morbidity
Time Frame: From time of birth of baby to six weeks postnatal.
e.g. seizures, birth asphyxia defined by trialists, neonatal encephalopathy, disability in childhood, Proven and suspected neonatal sepsis
From time of birth of baby to six weeks postnatal.
Apgar score < 7 at five minutes.
Time Frame: From birth of baby to five minutes of life.
The Apgar score provides an accepted and convenient method for reporting the status of the newborn infant immediately after birth and the response to resuscitation if needed (ACOG 2015).
From birth of baby to five minutes of life.
Cord PH < 7.20
Time Frame: From birth of infant to collection of cord bloods after delivery of the placenta (an average of 15 minutes)
Umbilical cord blood gas test.
From birth of infant to collection of cord bloods after delivery of the placenta (an average of 15 minutes)
Neonatal encephalopathy
Time Frame: From time of birth to six weeks postnatal.
Severity of hypoxic ischaemic encephalopathy assessed using Sarnat staging; i)Stage 1 (mild): hyper-alertness, hyper-reflexia, dilated pupils, tachycardia, absence of seizures; ii)Stage 2 (moderate): lethargy, hyper-reflexia, miosis, bradycardia, seizures, hypotonia with weak suck and Moro reflexes; iii)Stage 3 (severe): stupor, flaccidity, small to mid-position pupils which react poorly to light, decreased stretch reflexes, hypothermia and absent Moro reflex.
From time of birth to six weeks postnatal.
Perinatal death
Time Frame: From time of randomisation to seven completed days after birth of baby (up to 6 weeks)
The perinatal period is defined as "commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth of baby."
From time of randomisation to seven completed days after birth of baby (up to 6 weeks)
Admission to neonatal intensive care unit or equivalent
Time Frame: From time of birth to six weeks postnatal.
Admission of infant to neonatal intensive care unit or equivalent
From time of birth to six weeks postnatal.
Length of time from membrane sweep to birth of baby.
Time Frame: From time of membrane sweep to birth of baby (up to 4 weeks)
Length of time from membrane sweep to birth of baby .
From time of membrane sweep to birth of baby (up to 4 weeks)
Length of time from formal induction of labour to birth of baby.
Time Frame: From time of formal induction of labour to birth of baby (up to 2 weeks)
Length of time from formal induction of labour to birth of baby.
From time of formal induction of labour to birth of baby (up to 2 weeks)
Overall length of maternal hospital stay
Time Frame: From time of randomisation to six weeks postnatal (up to 11 weeks).
Overall length of maternal hospital stay
From time of randomisation to six weeks postnatal (up to 11 weeks).
Length of infant stay in neonatal intensive care unit or equivalent
Time Frame: From time of birth to six weeks postnatal.
Length of infant stay in neonatal intensive care unit or equivalent
From time of birth to six weeks postnatal.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

July 30, 2020

Primary Completion (ANTICIPATED)

March 30, 2021

Study Completion (ANTICIPATED)

December 30, 2021

Study Registration Dates

First Submitted

January 17, 2020

First Submitted That Met QC Criteria

March 10, 2020

First Posted (ACTUAL)

March 13, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 14, 2020

Last Update Submitted That Met QC Criteria

May 12, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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