Feasibility study protocol of a pragmatic, randomised controlled pilot trial: membrane sweeping to prevent post-term pregnancy-the MILO Study

Elaine M Finucane, Linda Biesty, Deirdre Murphy, Amanda Cotter, Eleanor Molloy, Martin O'Donnell, Shaun Treweek, Paddy Gillespie, Marian Campbell, John J Morrison, Alberto Alvarez-Iglesias, Gill Gyte, Declan Devane, Elaine M Finucane, Linda Biesty, Deirdre Murphy, Amanda Cotter, Eleanor Molloy, Martin O'Donnell, Shaun Treweek, Paddy Gillespie, Marian Campbell, John J Morrison, Alberto Alvarez-Iglesias, Gill Gyte, Declan Devane

Abstract

Background: Post-term pregnancy is associated with an increased risk of maternal complications, respiratory distress and trauma to the neonate. Amniotic membrane sweeping has been recommended as a simple procedure to promote the spontaneous onset of labour. However, despite its widespread use, there is an absence of evidence on (a) its effectiveness and (b) its optimal timing and frequency. 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 foetus ≥ 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 versus weekly sweep. The proposed feasibility study consists of four work packages, i.e. (1) a multicentre, pilot randomised trial; (2) a health economic analysis; (3) a qualitative study; and (4) a study within the host trial (a SWAT). Outcomes to be collected include recruitment and retention rates, compliance with protocol, randomisation and allocation processes, attrition rates and cost-effectiveness. Focus groups will be held with women and clinicians to explore the acceptability and feasibility of the proposed intervention, study procedures and perceived barriers and enablers to recruitment.

Discussion: 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. Results will inform whether and how the design of the definitive trial as originally envisaged should be delivered or adapted.

Trial registration: ClinicalTrials.gov NCT04307199 . Registered on 12 March 2020.

Keywords: Feasibility; Induction of labour; Membrane sweep; Pilot trial; Post-term; SWAT.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study design

References

    1. Bakker JJ, van der Goes BY, Pel M, Mol BW, van der Post JA. Morning versus evening induction of labour for improving outcomes. Cochrane Database Syst Rev. 2013;(2):CD007707. 10.1002/14651858.CD007707.pub2.
    1. World Health Organization . WHO recommendations: induction of labour at or beyond term. 2018.
    1. American College of Obstetricians and Gynecologists . Practice advisory - clinical guidance for integration of the findings of the ARRIVE Trial: labor induction versus expectant management in low-risk nulliparous women labor induction. 2018.
    1. Middleton P, Shepherd E, Morris J, Crowther CA, Gomersall JC. Induction of labour at or beyond 37 weeks’ gestation. Cochrane Database Syst Rev. 2020;7(7):CD004945. doi: 10.1002/14651858.CD004945.pub5.
    1. Grobman W, Rice M, Reddy U, Tita A, Silver R, Mallett G, Hill K, Thom E, El-Sayed Y, Perez-Delboy, Rouse D, Saade G, et al. A randomized trial of elective induction of labor at 39 weeks compared with expectant management of low-risk nulliparous women. Am J Obstet and Gynaecol. 2018;218(1):S601. doi: 10.1016/j.ajog.2017.12.016.
    1. The Society of Obstetricians and Gynaecologists of Canada . Induction of Labour SOGC Clinical Practice Guideline No. 296. 2013.
    1. Alfirevic Z, Gyte GML, Nogueira Pileggi V, Plachcinski R, Osoti AO, Finucane EM. Home versus inpatient induction of labour for improving birth outcomes. Cochrane Database Syst Rev. 2020;(8):CD007372. 10.1002/14651858.CD007372.pub4 Accessed 8 Jan 2021.
    1. Nippita T, Trevena J, Patterson J, Ford J, Morris J, Roberts C. Variation in hospital rates of induction of labour: a population-based record linkage study. BMJ Open. 2015;5(9):e008755. doi: 10.1136/bmjopen-2015-008755.
    1. Spong CY. Defining “term” pregnancy: recommendations from the Defining “Term” Pregnancy Workgroup. JAMA. 2013;309:2445–2446. doi: 10.1001/jama.2013.6235.
    1. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: final data for 2017. Natl Vital Stat Rep. 2018;67(8):1–50.
    1. American College of Obstetricians and Gynecologists . Management of late-term and postterm pregnancies. Practice Bulletin 16. 2014.
    1. Euro-Peristat project . European Perinatal Health Report. Core indicators of the health and care of pregnant women and babies in Europe in 2015. 2018.
    1. American College of Obstetricians and Gynecologists Management of late-term and postterm pregnancies: ACOG Practice Bulletin Number 146. Obstet Gynecol. 2014;124:390–396. doi: 10.1097/01.AOG.0000452744.06088.48.
    1. Heimstad RI, Romundstad PR, Salvesen KA. Induction of labour for post-term pregnancy and risk estimates for intrauterine and perinatal death. Acta Obstet Gynecol Scand. 2008;87(2):247–249. doi: 10.1080/00016340701743165.
    1. Hedegaard M, Lidegaard Ø, Wessel Skovlund C, Steinrud Mørch L, Hedegaard M. Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention. BMJ Open. 2014;4:e005785. doi: 10.1136/bmjopen-2014-005785.
    1. Alfirevic Z, Aflaifel N, Weeks A. Oral misoprostol for induction of labour. Cochrane Database Syst Rev. 2014;2014(6):CD001338. doi: 10.1002/14651858.CD001338.pub3.
    1. National Institute for Health and Care Excellence . Inducing labour. 2008.
    1. Caughey AB, Sundaram V, Kaimal AJ, Cheng YW, Gienger A, Little SE, Lee JF, Wong L, Shaffer BL, Tran SH, Padula A, McDonald KM, Long EF, Owens DK, Bravata DM. Maternal and neonatal outcomes of elective induction of labor. 2009.
    1. National Health Service Clinical guidelines . Management of artificial rupture of membranes. 2017.
    1. Smyth RMD, Markham C, Dowswell T. Amniotomy for shortening spontaneous labour. Cochrane Database Syst Rev. 2013;(6):CD006167. 10.1002/14651858.CD006167.pub4 Accessed 8 Jan 2021.
    1. de Vaan MDT, ten Eikelder MLG, Jozwiak M, Palmer KR, Davies-Tuck M, Bloemenkamp KWM, Mol BWJ, Boulvain M. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. 10.1002/14651858.CD001233.pub3 Accessed 8 Jan 2021.
    1. Boulvain M, Stan C, Irion O. Membrane sweeping for induction of labour. Cochrane Database Syst Rev. 2005;2005(1):CD000451. doi: 10.1002/14651858.CD000451.pub2.
    1. Blackburn S. Maternal, fetal, & neonatal physiology - a clinical perspective. 3. Missouri: Saunders Elsevier; 2013.
    1. Wong SF, Hui SK, Choi H, Ho LC. Does sweeping of membranes beyond 40 weeks reduce the need for formal induction of labour? BJOG. 2002;109:632–636. doi: 10.1111/j.1471-0528.2002.01193.x.
    1. Finucane EM, Murphy DJ, Biesty LM, Gyte GML, Cotter AM, Ryan EM, Boulvain M, Devane D. Membrane sweeping for induction of labour. Cochrane Database Syst Rev. 2020;(2):CD000451. 10.1002/14651858.CD000451.pub3 Accessed 8 Jan 2021.
    1. Delaney M, Roggensack A. The Society of Obstetricians and Gynaecologists of Canada. Clinical Practice Guidelines No. 214-Guidelines for the management of pregnancy at 41+0 to 42+0 weeks. J Obstet Gynaecol Canada. 2017;39(8):e164–e174. doi: 10.1016/j.jogc.2017.04.020.
    1. South Australian Maternal & Neonatal Clinical Network . Clinical guideline induction of labour techniques. 2014.
    1. Queensland Clinical Guidelines . Induction of labour. 2017.
    1. Montgomery AA, Peters TJ, Little P. Design, analysis and presentation of factorial randomised controlled trials. BMC Med Res Methodol. 2003;3:26. doi: 10.1186/1471-2288-3-26.
    1. Chan A-W, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin J, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleža-Jerić K, Laupacis A, Moher D. SPIRIT 2013 Explanation and Elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586.
    1. Hofmeyr GJ, Alfirevic Z, Kelly AJ, Kavanagh J, Thomas J, Neilson JP, et al. Methods for cervical ripening and labour induction in late pregnancy: generic protocol [protocol]. Cochrane Database Syst Rev. 2009;(3):CD002074. 10.1002/14651858.CD002074.pub2.
    1. World Health Organization . Maternal, newborn, child and adolescent health. 2019.
    1. Connelly LM. Pilot studies. Medsurg Nurs. 2008;17(6):411–412.
    1. Eldridge SM, Chan C, Campbell MJ, Bond CM, Hopewell S, Thabane L, Lancaster GA. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. doi: 10.1136/bmj.i5239.
    1. O’Cathain A, Hoddinott P, Lewin S, Thomas K, Young B, Adamson J, Jansen Y, Mills N, Moore G, Donovan JL. Maximising the impact of qualitative research in feasibility studies for randomised controlled trials: guidance for researchers. Pilot Feasibility Stud. 2015;1:32. doi: 10.1186/s40814-015-0026-y.
    1. Sandelowski M. Whatever happened to qualitative description? Res Nurs Health. 2000;23(4):334–340. doi: 10.1002/1098-240X(200008)23:4<334::AID-NUR9>;2-G.
    1. Ritchie J, Lewis J. Qualitative research practice: a guide for social science students and researchers. London: Sage Publications; 2003.
    1. Tooher R, Middleton PF, Crowther CA. A thematic analysis of factors influencing recruitment to maternal and perinatal trials. BMC Pregnancy Childbirth. 2008;8:36. doi: 10.1186/1471-2393-8-36.
    1. Frew P, Saint-Victor D, Brewinski Isaacs M, Kim S, Swamy GK, Sheffield JS, Edwards KM, Villafana T, Kamagate O, Ault K. Recruitment and retention of pregnant women into clinical research trials: an overview of challenges, facilitators, and best practices. Clin Infect Dis. 2014;59(Suppl 7):S400–S407. doi: 10.1093/cid/ciu726.
    1. Treweek S, Pitkethly M, Cook J, Fraser C, Mitchell E, Sullivan F, Jackson C, Taskila TK, Gardner H. Strategies to improve recruitment to randomised trials. Cochrane Database Syst Rev. 2018;(2):MR000013. 10.1002/14651858.MR000013.pub6.
    1. Chalmers I, Glasziou P. Avoidable waste in the production and reporting of research evidence. Lancet. 2009;374(9683):86–89. doi: 10.1016/S0140-6736(09)60329-9.
    1. Morgan B, Hejdenberg J, Hinrichs-Krapels S, Armstrong D. Do feasibility studies contribute to, or avoid, waste in research? PLoS One. 2018;13(4):e0195951. doi: 10.1371/journal.pone.0195951.
    1. Sampat BN, Lichtenberg FR. What are the respective roles of the public and private sectors in pharmaceutical innovation? Health Aff (Millwood) 2011;30(2):332–339. doi: 10.1377/hlthaff.2009.0917.
    1. National Institutes of Health . U.S. Department of Health & Human Services. 2019.
    1. National Institute for Health Research . NIHR Annual Report 2015-16. 2017.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe