Lateral Episiotomy or Not in Vacuum Assisted Delivery in Non-parous Women (EVA)

• ClinicalTrials.gov Identifier: NCT02643108
• Recruitment Status: Recruiting
• First Posted: December 30, 2015
• Last Update Posted: October 8, 2020
• Sponsor: Karolinska Institutet
• Collaborator: The Swedish Research Council
• Information provided by (Responsible Party): Sophia Brismar Wendel, Karolinska Institutet

Tracking Information

• First Submitted Date: December 28, 2015
• First Posted Date: December 30, 2015
• Last Update Posted Date: October 8, 2020
• Actual Study Start Date: June 30, 2017
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2020)

Obstetric anal sphincter injury [ Time Frame: 1 hour ]

Rupture or tear of the external and/or internal anal sphincter at any degree (third and fourth degree perineal tear); International Classification of Diseases (ICD)-10 O70.2 or O70.3.

Original Primary Outcome Measures (submitted: December 28, 2015)

Obstetrical anal sphincter injury [ Time Frame: 1 hour ]

Rupture or tear of the external and/or internal anal sphincter at any degree (third and fourth degree perineal tear); International Classification of Diseases (ICD)-10 O70.2 or O70.3.

Current Secondary Outcome Measures (submitted: October 3, 2020)

• Other degree of perineal or vaginal tear [ Time Frame: 1 hour ]
  Rupture, tear or hematoma in the perineum or vagina; International Classification of Diseases (ICD)-10 O70.0, O70.1, O70.9, O71.4-9.
• Maternal blood loss at delivery [ Time Frame: 6 hours ]
  Estimated blood loss in milliliters through weighing of sheets and drapes during and up to 6 hours after delivery.
• Neonatal scalp injury [ Time Frame: 24 hours ]
  Prevalence (number of patients) of scalp injury to the neonate after instrumental delivery, such as open wounds, cephalic hematoma, subgaleal hematoma, and intracranial hemorrhage, according to diagnose by neonatologist.
• Pain experience [ Time Frame: 1 day, 8 weeks, 1 year ]
  VAS (0-10) estimated pain through questionnaire at baseline (first days post partum), 8 weeks and 12 months after delivery and at 8 weeks through questionnaires: number of days using analgetic medication.
• Birthing experience [ Time Frame: 8 weeks ]
  Questionnaire at 8 weeks after delivery regarding patient satisfaction using the Birth Satisfaction Scale Revised (short form) and the Childbirth Experience Questionnaire 2.0.
• Anal incontinence [ Time Frame: 8 weeks, 1 year, and 5 years ]
  Questionnaire at baseline, 8 weeks, 1 year, and 5 years after delivery through the Swedish Obstetrical Tear Register regarding anal continence function (Wexner score based).
• Sexual function [ Time Frame: 1 year and 5 years ]
  Questionnaire at baseline (first day post partum), 1 year, and 5 years after delivery through the Swedish Obstetrical Tear Register, as well as FSFI and FSDS Questionnaires.
• Pelvic organ prolapse symptoms [ Time Frame: 1 year and 5 years ]
  Questionnaire at baseline, 1 year, and 5 years after delivery through the Swedish Obstetrical Tear Register regarding symptoms of pelvic organ prolapse.
• Quality of life score [ Time Frame: 1 year and 5 years ]
  Assessment of quality of life by questionnaire at baseline, 1 year, and 5 years using the Euro-QoL-5D
• Mode of delivery in subsequent birth [ Time Frame: 5 years and 10 years ]
  Register data will be extracted from the Swedish Pregnancy Register.
• Prevalence of obstetric anal sphincter injury in subsequent birth [ Time Frame: 5 years and 10 years ]
  Register data will be extracted from the Swedish Pregnancy Register.
• Prevalence of episiotomy in subsequent birth [ Time Frame: 5 years and 10 years ]
  Register data will be extracted from the Swedish Pregnancy Register.

Original Secondary Outcome Measures (submitted: December 28, 2015)

• Second degree perineal or vaginal tear [ Time Frame: 1 hour ]
  Rupture, tear or hematoma in the perineum or vagina; International Classification of Diseases (ICD)-10 O70.1, O70.9, O71.4-9.
• Pain short term [ Time Frame: 2 months ]
  Questionnaire at 8 weeks after delivery through the Swedish Obstetrical Tear Registry regarding number of days using analgetic medication.
• Anal incontinence [ Time Frame: 1 year ]
  Questionnaire at 8 weeks and 1 year after delivery through the Swedish Obstetrical Tear Registry regarding anal continence function (Wexner score based).
• Sexual function [ Time Frame: 1 year ]
  Questionnaire at 1 year after delivery through the Swedish Obstetrical Tear Registry regarding sexual function.
• Birthing experience [ Time Frame: 2 months ]
  Questionnaire at 8 weeks after delivery regarding patient satisfaction using the Birth Satisfaction Scale short form.
• Maternal blood loss at delivery [ Time Frame: 6 hours ]
  Estimated blood loss in milliliters through weighing of sheets and drapes during and up to 6 hours after delivery.
• Neonatal scalp injury [ Time Frame: 24 hours ]
  Scalp injury to the neonate after instrumental delivery, such as open wounds, cephalic hematoma, subgaleal hematoma, and intracranial hemorrhage.
• Pelvic organ prolapse symptoms [ Time Frame: 1 year ]
  Questionnaire at 1 year after delivery through the Swedish Obstetrical Tear Registry regarding symptoms of pelvic organ prolapse.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lateral Episiotomy or Not in Vacuum Assisted Delivery in Non-parous Women
• Official Title: Randomized Controlled Clinical Trial of Lateral Episiotomy Versus no Episiotomy in Vacuum Assisted Delivery in Non-parous Women
• Brief Summary: Nulliparous women with a live singleton pregnancy in cephalic presentation past 34 gestational weeks will be randomized to lateral episiotomy or no episiotomy when operative vaginal delivery by vacuum extraction is indicated. Primary outcome is clinically diagnosed obstetric anal sphincter injury (OASIS) of any degree.

Detailed Description

The study has started at Danderyd Hospital. Danderyd Hospital is a large teaching hospital affiliated to the Karolinska Institute in Stockholm, Sweden. South General Hospital in Stockholm, Uppsala University Hospital, Falun Hospital, Helsingborg Hospital, Växjö Hospital, Umeå University Hospital, and Gothenburg University Hospital Östra have joined the trial 2017-2019.

Informed consent is collected from nulliparous women with a singelton, live fetus in cephalic presentation, with a planned vaginal delivery and without previous gynecological surgery due to incontinence or genital prolapse. Women can be approached at any time from gestational week 18 until delivery, unless they are in severe pain or discomfort, there is not enough time to consider the information, or any other reason not to obtain consent. The informed consent form is kept at the receiving research department and a note of consent/no consent is made in the obstetric medical file.

At indication for vacuum extraction, the patient's consent is confirmed verbally and allocation is made by sealed opaque envelopes on the vacuum extraction equipment mobile cart. Randomization is performed 1:1 in random permuted blocks generated by an external organization (Karolinska Trial Alliance).

Lateral episiotomy is performed according to the intervention description. A reduction of OASIS from 12.4% to 6.2% can be detected with 80% power and less than 5% risk of alpha-error (p<0.05) with 354 women in each group using Chi-square test comparing two independent proportions in a two-sided test (3% missing outcome). A smaller reduction is clinically valuable, although the risk-benefit relationship between receiving a prophylactic episiotomy and the chance of an intact perineum may limit the feasibility of a larger trial in a setting with a restrictive episiotomy policy. We have obtained ethical approval to randomise a total of 1400 women, which enables us to detect a reduction in OASIS rate at VE from 12.4% to 7.8% (p<0.05). We will perform an interim analysis in order to exclude an unethically large difference (p<0.01) in primary outcome or serious adverse events at 350 randomized women.

Data is collected prospectively through Case Record Forms and the obstetric medical file Obstetrix (Cerner Sverige AB), which covers approximately 98% of deliveries with complete data, and the Swedish Pregnancy Register covering the whole of Sweden from 2015. Using a weblink, questionnaires from the national Perineal Tear Register, are sent out electronically for the follow-up of the study participants. In addition, questionnaires regarding birth satisfaction (BSS-R and CEQ 2.0) are sent at 8 weeks after delivery. Questionnaires regarding sexual function (FSFI and FSDS) and quality of life (Euro-QoL-5D) at delivery and after 12 months.

A follow-up from registers regarding mode of delivery and prevalence of episiotomy and OASIS in subsequent births will be performed at 5 years and 10 years after the index birth.

A substudy takes place in Stockholm, Uppsala, and Helsingborg, where included (randomized) women are examined at 6-12 months after delivery with 2D and 3D endovaginal and anal ultrasound to detect levator and sphincter injuries, measure episiotomy scars, establish POP-Q scores, and evaluate a new questionnaire for pelvic floor function after perineal tears.

Another substudy takes place in Stockholm and Falun, where women who have been asked for consent (both affirmative and non-affirmative responders) as well as midwives who have tried to obtain consent, are invited to a qualitative interview study to explore the recruitment experience of women and midwives.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:

The allocation will be masked during statistical analyses.

Primary Purpose: Prevention

Condition

• Pelvic Floor Disorders
• Fecal Incontinence
• Dystocia
• Fetal Hypoxia

Intervention

Procedure: Lateral episiotomy

When the woman is randomized to episiotomy, lateral episiotomy is performed with scissors on the left or right side of the vaginal opening. Origin of incision is 1.0 - 3.0 cm from the midline/posterior forchette and is cut 3.0 cm or more towards the ischial tuberosity at an angle of 60 degrees from the midline.

Study Arms

• Experimental: Lateral episiotomy
  Lateral episiotomy (left or right) is performed by the attending physician or assisting midwife at crowning of the fetal head in operative vaginal delivery by vacuum extraction. Regular manual perineal support is applied.
  Intervention: Procedure: Lateral episiotomy
• No Intervention: No episiotomy
  No episiotomy is performed during operative vaginal delivery, unless vitally indicated (for example severe fetal distress). The woman may tear spontaneously. Regular manual perineal support is applied.

Publications *

• Laine K, Pirhonen T, Rolland R, Pirhonen J. Decreasing the incidence of anal sphincter tears during delivery. Obstet Gynecol. 2008 May;111(5):1053-7. doi: 10.1097/AOG.0b013e31816c4402.
• Murphy DJ, Macleod M, Bahl R, Goyder K, Howarth L, Strachan B. A randomised controlled trial of routine versus restrictive use of episiotomy at operative vaginal delivery: a multicentre pilot study. BJOG. 2008 Dec;115(13):1695-702; discussion 1702-3. doi: 10.1111/j.1471-0528.2008.01960.x.
• Kalis V, Laine K, de Leeuw JW, Ismail KM, Tincello DG. Classification of episiotomy: towards a standardisation of terminology. BJOG. 2012 Apr;119(5):522-6. doi: 10.1111/j.1471-0528.2011.03268.x. Epub 2012 Feb 3. Review.
• de Leeuw JW, de Wit C, Kuijken JP, Bruinse HW. Mediolateral episiotomy reduces the risk for anal sphincter injury during operative vaginal delivery. BJOG. 2008 Jan;115(1):104-8. Epub 2007 Nov 12.
• Räisänen SH, Vehviläinen-Julkunen K, Gissler M, Heinonen S. Lateral episiotomy protects primiparous but not multiparous women from obstetric anal sphincter rupture. Acta Obstet Gynecol Scand. 2009;88(12):1365-72. doi: 10.3109/00016340903295626.
• Bergendahl S, Ankarcrona V, Leijonhufvud Å, Hesselman S, Karlström S, Kopp Kallner H, Brismar Wendel S. Lateral episiotomy versus no episiotomy to reduce obstetric anal sphincter injury in vacuum-assisted delivery in nulliparous women: study protocol on a randomised controlled trial. BMJ Open. 2019 Mar 13;9(3):e025050. doi: 10.1136/bmjopen-2018-025050.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 24, 2019): 710
• Original Estimated Enrollment (submitted: December 28, 2015): 700
• Estimated Study Completion Date: December 31, 2030
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Nulliparous women,18 years old or more, able to give written informed consent in Swedish or English, with a live singleton pregnancy, in a cephalic presentation over 34 completed gestational weeks with a medical indication of vacuum extraction.

Exclusion Criteria:

• Previous vaginal or perineal surgery for incontinence or genital prolapse, any contra-indication to vacuum extraction (ie fetal disorder or malformation).

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sophia Brismar Wendel, MD, PhD; +46812358564; sophia.brismar-wendel@sll.se

Contact: Maria Persson, MD, PhD; +46812355000; maria.k.persson@sll.se

• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT02643108
• Other Study ID Numbers: 2015/1238-31/2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Anonymized data on the primary outcome will be shared with other researchers for a joint publication.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When results have been published (after 1 year).
• Access Criteria: Anonymized data on the primary outcome will be shared with other researchers for a joint publication.

• Responsible Party: Sophia Brismar Wendel, Karolinska Institutet
• Study Sponsor: Karolinska Institutet
• Collaborators: The Swedish Research Council

Investigators

• Principal Investigator: Sophia Brismar Wendel, MD, PhD; Karolinska Institutet Danderyd Hospital

• PRS Account: Karolinska Institutet
• Verification Date: October 2020