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

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.