The PLUS Study: Comparison of VicrylPlus® Versus Vicryl® for Repair of Perineal Tears

Study Overview
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Brief Summary
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INTRODUCTION It is estimated that over 80% of women who give vaginal birth will sustain some form of perineal tear and of these 60-70% will require suturing. It is of great importance that operators are familiar with the best suturing technique and suture material in order to minimize possible associated short- and long-term sequelae. There is evidence for suturing continuously to reduce postoperative pain and superficial dyspareunia, but the choice of suture-material is still debated. The function of a suture is to close the wound to minimize the bleeding, the risk for infection and to adapt the wound edges to promote anatomic correct healing. Infection results in softened wound edges, shirked sutures, pain and dehiscence. Delayed and/or compromised wound healing is correlated with impaired strength in the affected tissue. Reported frequency of infection after first and second degree tear is between 1 and 11% where the discrepancy most likely is due to poor registration and follow-up. In 2004 Polyglactin 910 was launched with a new antibacterial coating of Triclosan (VicrylPlus®). Studies suggest a correlation between the use of VicrylPlus® and a reduction of up to 30% of surgical site infections (SSI) compared to conventional sutures in a non-colonized wound. OBJEKTIVE: The primary objective is to compare infection rates and pain intensity when using Vicryl® versus VicrylPlus® for perineal repair after delivery. Secondly, to show if there is a difference in sequelae (pelvic floor dysfunction) after one year between the two groups. METHODS The participants are randomly allocated to continuously suturing with either Vicryl® or VicrylPlus®. Sealed identical-looking envelopes are prepared and placed in the delivery room (randomized into blocks of 50) containing randomization number, sutures, declaration of informed consent and questionnaires. The participants are instructed to fill in the first questionnaire after 7 days and the second questionnaire after 8 weeks post partum. After 8 weeks all participants are offered a routine visit to the out-patient clinic. After one year an internet-based survey will be sent out to the participants. In case of complains/signs of deficient healing after one year, the woman will be offered a clinical control. Data will be analyzed according to intention to treat and per-protocol.

Detailed Description
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HYPOTHESIS: VicrylPlus® is superior to Vicryl® in terms of infection rate, delayed perineal wound healing and short-/longterm perineal discomfort. Methods: Women given birth at Skåne University hospital after November 23, 2015 are assessed for eligibility. The hospital consist of two labor wards with approximately 9.000 deliveries pr year. After birth and in case of a first, second or third degree tear, the labor-responsible midwife or doctor prepares the patient for the required suture procedure. The two sutures used in this project are not new to the staff, before the beginning of the study both sutures were available on the delivery rooms and randomly used dependent on the midwife's/doctor's preference. Also, before study-start all midwifes/doctors were carefully instructed in detection and classification of perineal tears and the corresponding suturing technique. There is evidence for suturing deep and long tears in the vagina and tears in perineum continuously why we have educated and trained our staff to suture by this technique (e-learning and practical training). Tears will be sutured mainly by midwives and in case of doctor assistance this will be recorded in the obstetrical chart. The delivery course, degree of laceration, suture-procedure are always documented in our electronic obstetrical record accordingly to predefined standards (Obstetrix, Siemens). If the woman is enrolled in the study the randomization number will be incorporated in the operation description. After identification of a tear requiring continuously suturing (and not only a few stitches) the personal will kindly ask the woman to participate in the study. The woman will be introduced to the reason for conducting the study and to the questions. If she do not agree or is unable for enrollment, or if the midwife is un-certified in continuously suturing, the midwife can choose the suture she usually prefers. If the woman agrees, she will be randomly allocated to suturing with either Vicryl® or VicrylPlus®, CT-1, 2/0 gauge by drawing a sealed pre-packed and identical looking envelope whereafter written informed consent will be obtained. The envelope contains the randomization number (randomized into blocks of 50 by Randomization.com), two packets of identical sutures, an envelope to the patient with the questionnaires and a prepaid returning envelope. The type of suture will be blinded for the participants and for possible contacts to medical staff after discharge, but not to the suturing midwife/doctor who is carefully instructed not to disclose the origin of the suture used. If there is need for more than 2 sutures the staff can bring more material from our sterile depot. Randomization number, the woman's personal number and the woman's and the operator's signature are all noted on the written patient consent. The document will be returned to a locked box. Once in a week the responsible investigator (Nana Wiberg) empties the box. The randomization number, date of inclusion, personal number, telephone number will be noted by NW in the specific study protocol to which only Kristine Lund Sønnichsen (KLS) and NW have access. The informed consent will thereafter be placed into a locked cabinet. The patient is instructed to fill in the questionnaire at respectively 7 days and 8 weeks postpartum and in the meantime bring it with her, in case of a clinical control. The questionnaire consists of a general information sheet where the woman fills in information about education, body mass index (BMI), previous and actual pregnancy and deliveries. The other sheet consists of a visual analogue scale (VAS scale), questions about eventually use of painkillers and signs-of-infection questions accordingly to the CDC criteria. The third part is only used in case of contact with medical staff after discharge. All non-respondents will be contacted primarily by telephone and secondarily by sending a reminding letter by one of the investigators (KLS or NW) if the questionnaire is not received within a week after expected deadline (calculated from date of inclusion). When the questionnaire is received the answers are noticed together with the obstetrical data of interest in the study protocol by one of the investigators (KLS). All obstetrical data are extracted from the same database (Obstetrix). After one year the patient will be asked to fill in an electronic internet based survey and in case of complains/symptoms of deficient healing the woman will be invited to a clinical control. Statistics Calculation The sample size to detect a 50% reduction in infections from an estimated prevalence of 10% gives 474 participants in each arm to detect this difference with 80% power at 5% significance level, two tailed. Data will be analyzed according to intention to treat and per-protocol. Continuous variables will be presented as mean ± standard deviation, median, range and categorical variables as number (percentage). For comparison between groups following test will be used; the unpaired t-test for continuous normally distributed data, the Mann-Whitney U-test for continuous skew distributed data and the χ2 test for categorical variables. Frequency data will be presented as odds ratios with 95% confidence interval. Spearman's rank correlation will be used to analyze correlations between continuous variables. P < 0.05 is considered statistically significant. The IBM Statistical Package for Social Sciences, Windows version 22 will be used (SPSS, Inc., Chicago, IL, USA) for statistical analysis. The CONSORT 2010 Statement will be met. An independent steering committee will conduct interim analysis after 800 inclusions to estimate when to close the study. Women in need of continuously suturing but not included in the study are noticed in the protocol. Women included but not answering the questionnaire is considered to be a part of the trial. A flow chart will be used to visualize the study group/exclusions and dropouts. Ethical aspects The study is approved by the local ethical board, Lund, Sweden (Dnr 2015/10). Sideeffects There is no reason to believe that this study will inflict any harm or any other side effects to the participants or the operator. Triclosan is approved by FDA (U.S. Food and Drug Administration) and there are no reports or evidence for any side effects including allergic reactions or induction of antibiotic resistance.

Official Title
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Comparison of VicrylPlus® Versus Vicryl® for Surgical Repair of Perineal Tears; a Prospectively Randomized Controlled Trial

Conditions
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Skin Structures and Soft Tissue Infections, Wound Infection

Intervention / Treatment
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* Device: VicrylPlus®
* Device: Vicryl®


Participation Criteria
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Eligibility Criteria
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Inclusion Vaginal delivery complicated by a spontaneously first, second or third degree tear with need of continuously suturing Woman with episiotomy Able to read and understand Swedish Exclusion Previously perineal surgery other than primary repair after delivery Birth of a stillborn infant HIV or active Hepatitis B/C infection Severe perineal warts or varicose veins The operator is uncomfortable with continuous suturing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vicryl®<br>The vaginal or and perineal tear is sutured continuously with Vicryl®. The instruments for suturing and the bedcover are clean whereas the gloves are sterile. | Device: Vicryl®<br>* Suture<br>|
| Active Comparator: VicrylPlus®<br>The vaginal or and perineal tear is sutured continuously with VicrylPlus®. The instruments for suturing and bedcover are clean whereas the gloves are sterile. | Device: VicrylPlus®<br>* Suture<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of wound infection in vaginal and perineal tears after suturing with normal braided suture (Vicryl®) versus antibacterial braided suture (VicrylPlus®). | Presence of infection determined by a certified physician according to CDC's Criteria for Defining a Surgical Site Infection. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in self-reported pain after suturing vaginal and perineal tears with normal braided or antibacterial braided suture. | The woman is instructed to fill in the VAS scale (visual analog scale) | 8 weeks | 
| Number of patients who need or are resutured within one year after delivery for each suture | From EMR these data will be retrieved | one year after delivery | 
| Number of patients with superficial/deep dyspareunia or pelvic floor dysfunction one year after delivery for each suture | The participants will be asked to fill in a questionnaire | one year after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perineal tear, Labor, Triclosan