Post-operative Pain in Patients Undergoing Caesarean Section: Randomised Trial Evaluating Three Methods of Fascial Closure
Phase: NA
Conditions: Pregnancy Related, Cesarean Section, Post-operative Pain, Fascial Closure, Surgical Technique
Sponsor: Sunnybrook Health Sciences Centre

Protocol Number: FAS-101 
Version 1.0 - 25 November, 2020 
 
 
Evaluation of the impact of fascial closure technique on post-
operative pain in patients undergoing Pfannenstiel incision for 
Caesarean Section:  
A Randomised Trial 
 
Protocol 
 
Sponsor: 
 
DAN Women and Babies Unit 
Sunnybrook Health Sciences Centre 
2075 Bayview Avenue, Toronto, ON 
M4N 3M5 
 
 
Conduct: This clinical trial is being conducted in accordance with International Conference of 
Harmonisation guidelines on Good Clinical Practice and the ethical principles originated from the 
Declaration of Helsinki. It is confirmed that the Clinical Trial Protocol meets the applicable regulatory 
requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Contact List 
 
Sponsor: 
DAN Women and Babies Unit 
Sunnybrook Health Sciences Centre 
2075 Bayview Avenue, Toronto, ON 
Canada, M4N 3M5 
 
Principle Investigator: 
 
Dr. Richard Pittini, MD, MEd, FRCSC, FACOG 
Staff Physician, Associate Professor 
Department of Obstetrician and Gynaecologist, Sunnybrook Health Sciences Centre 
 
Sunnybrook Health Sciences Centre, Room C712 
2075 Bayview Avenue, Toronto, ON 
Canada, M4N 3M5 
 
E-mail: Richard.Pittini@Sunnybrook.ca 
Phone: 416-480-4579 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
Principle Investigator’s Agreement……………………………………………………………………………… 4 
Protocol Synopsis………………………………………………………………………………………………………… 5 
List of Abbreviations……………………………………………………………………………………………………. 7 
1. Background………………………………………………………………………………………………………. 8 
2. Study Rationale………………………………………………………………………………………………… 8 
2.1  
Hypothesis…………………………………………………………………………………. 9 
3. Study Aims……………………………………………………………………………………………………….. 9 
 
 
3.1  
Primary Objectives…………………………………………………………………….. 9 
 
 
3.2  
Secondary Objectives…………………………………………………………………. 9 
4. Study Design…………………………………………………………………………………………………….. 9 
4.1 
Study Overview…………………………………………………………………………. 9 
4.2 
Strengths and Limitations…………………………………………………………… 9 
5. Subject Selection………………………………………………………………………………………………. 10 
5.1 
Study Population……………………………………………………………………….. 10 
5.2 
Study Sample…………………………………………………………………………….. 10 
5.3 
Inclusion Criteria……………………………………………………………………….. 10 
5.4 
Exclusion Criteria……………………………………………………………………….. 10 
6. Proposed Interventions……………………………………………………………………………………. 10 
7. Study Treatments………………………………………………………………………………………………11 
7.1 
Method of Assigning Subjects to Treatment Groups………………….. 11 
7.2 
Blinding…………………………………………………………………………………….. 11 
7.3 
Data collection method……………………………………………………………… 11 
8. Withdrawal of Subjects From The Study…………………………………………………………… 11 
9. Data Safety Monitoring……………………………………………………………………………………. 13 
10. Statistical Methods and Considerations……………………………………………………………. 13 
10.1 
Demographic and Baseline Characteristics…………………………………. 13 
10.2 
Statistical Analysis……………………………………………………………………… 13 
11. Data Collection, Retention and Monitoring………………………………………………………. 13 
11.1 
Data Collection Instruments………………………………………………………. 13 
11.2 
Data Management Procedures………………………………………………….. 14 
11.3 
Data Quality Control and Reporting…………………………………………… 14 
11.4 
Archival of Data…………………………………………………………………………. 14 
11.5 
Availability and Retention of Investigational Records………………… 14 
11.6 
Monitoring………………………………………………………………………………… 15 
11.7 
Subject Confidentiality………………………………………………………………. 15 
12. Administrative, Ethical, Regulatory Considerations…………………………………………… 15 
12.1 
Protocol Amendments……………………………………………………………….. 15 
12.2 
Institutional Review Boards and Independent Ethics Committees 15 

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12.3 
Informed Consent Form……………………………………………………………… 16 
12.4 
Publications……………………………………………………………………………….. 17 
12.5 
Investigator Responsibilities………………………………………………………. 17 
13. References……………………………………………………………………………………………………….. 18 
14. Appendix A: Informed Consent Form……………………………………………………………….. 19 
15. Appendix B: Figures Showing Methods of Fascial Closure…………………………………. 24 
16. Appendix C: Pain Survey Questionnaire……………………………………………………………..27 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Principle Investigator’s Agreement 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties include 
ensuring the safety of the study subjects enrolled under my supervision and providing the DAN Women 
and Babies Unit with complete and timely information, as outlined in the protocol.  It is understood that 
all information pertaining to the study will be held strictly confidential and that this confidentiality 
requirement applies to all study staff at this site. Furthermore, on behalf of the study staff and myself, I 
agree to maintain the procedures required to carry out the study in accordance with accepted GCP 
principles and to abide by the terms of this protocol. 
 
Protocol Number: FAS-101 
 
Protocol Title: Evaluation of the impact of fascial closure technique on post-operative pain in patients 
undergoing Pfannenstiel incision for Caesarean Section:  
A Randomised Trial 
 
Protocol Date: 25 November 2020 
 
Principle Investigator: 
Dr. Richard Pittini, MD, MEd, FRCSC, FACOG 
Staff Physician, Associate Professor 
Department of Obstetrics and Gynaecology, University of Toronto 
Sunnybrook Health Sciences Centre 
DAN Women and Babies Unit 
2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5 
 
 
 
 
 
_________________________________ 
 
_______Nov. 26, 2020________________ 
Signature of Principle Investigator 
 
 
 
Date 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
 
TITLE 
Evaluation of the impact of fascial closure technique on post-
operative pain in patients undergoing Pfannenstiel incision for 
Caesarean Section:  
A Randomised Trial 
SPONSOR 
DAN Women and Babies Unit, Sunnybrook Health Sciences Centre 
FUNDING 
ORGANISATION 
DAN Women and Babies Unit, Sunnybrook Health Sciences Centre 
NUMBER OF SITES 
1 
RATIONALE 
Caesarean sections are the most commonly performed surgical 
procedure throughout the world. Within the Canadian population, 
approximately one-third of all deliveries occur via Caesarean 
section. Chronic pain post-operatively has been identified as an 
issue that a large proportion of patients suffer with. As a result, a 
variety of surgical techniques have been undertaken, with some 
being compared to ascertain the reason for this chronic pain. One 
method which has been observed is related to the fascial layer and 
associated pain related to this layer. Whilst the abdominal fascia 
plays an integral role in ensuring the abdominal contents remain in 
situ. A variety of methods have been employed and studied to 
ensure the integrity of the fascial layer to reduce the risk of 
dehiscence, but no studies undertaken to date have evaluated the 
method of fascial closure and their effect on post-operative pain. 
STUDY DESIGN 
Randomised, double-blind, three-arm trial 
PRIMARY OBJECTIVES 
1. Analgesia use  
2. Pain score between three groups 
NUMBER OF SUBJECTS 
350 
SUBJECT SELECTION 
Inclusion Criteria: 
- 
Women aged 18-60 years 
- 
Women with singleton pregnancy 
- 
Patient undergoing elective lower segment Caesarean section 
via a Pfannenstiel Incision 
- 
Use of Regional Anaesthesia (epidural or spinal anaesthesia) 
Exclusion Criteria: 
- 
Multiple pregnancy 
- 
Patient undergoing non-elective Caesarean section 
- 
Caesarean section through midline laparotomy incision 
- 
Patients undergoing Caesarean section under General 
Anaesthesia 
- 
History of chronic pain 
- 
History of post-operative complications (haematoma, abscess, 
dehiscence, re-operation) 

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ARMS AND 
INTERVENTIONS 
Participants will be blinded to which method of fascial closure will 
be undertaken at the time of their surgery. 
1. Single suture, knot above rectus fascia 
2. Two sutures, knots above rectus fascia 
3. Two sutures, buried knots below rectus fascia 
DURATION OF SUBJECT 
PARTICIPATION AND 
DURATION OF STUDY 
Subjects will be enrolled in the study for 10 weeks. 
Screening: 1 day 
Treatment: 1-2 days (subjects will be admitted to hospital) 
Follow-up: 10 weeks 
The total duration of subject recruitment time is 6 months, with 
subsequent follow-up over a 10-week period after initial 
recruitment. 
EFFICACY 
EVALUATIONS 
 
PRIMARY ENDPOINT 
1. Analgesia use in first 72-hour period post-operatively. 
2. Pain score questionnaire results over 10-week post-operative 
period. 
STATISTICS 
 
Primary Analysis Plan 
Statistical analysis will be undertaken using IMB® SPSS® Statistical 
Software ver. 26 to undertake a two-sided T-test comparing group 
1 vs. 2 and group 1 vs. 3 to assess for statistical significance in 
analgesia use and pain scores. 
Rationale for Number 
of Subjects 
Based on a power of 80% at an alpha of 0.05, we estimate a 15% 
reduction in pain scores. As a result, we require a total of 255 
subjects in this study. Given an estimated drop-out rate of 35%, we 
aim to recruit a total of 350 participants. 
In addition, sub-group analysis will be undertaken comparing pain 
scores between primary and repeat Caesarean sections. Based on 
the same power of 80% at an alpha of 0.05, with an estimation of a 
15% difference in pain scores, we require a total of 140 subjects for 
this sub-group analysis. 
 
 
 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS 
 
CS 
 
Caesarean section 
CPCSP  
Chronic Postsurgical Caesarean Section Pain 
CPSP  
Chronic Postsurgical Pain 
CSEA  
Combined Spinal-Epidural Anaesthesia 
DSMB  
Data Safety Monitoring Board 
eCRF  
Electronic Case Report Form 
EPCS  
Elective Primary Caesarean Section 
ERCS  
Elective Repeat Caesarean Section 
GCP 
 
Good Clinical Practice 
ICF 
 
Informed Consent Form 
IEC 
 
Independent Ethics Committee 
IRB 
 
Institutional Review Board 
LSCS 
 
Lower segment Caesarean section 
PI 
 
Principle Investigator 
SAP 
 
Statistical Analysis Plan 
VAS 
 
Visual Analogue Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
BACKGROUND 
 
Caesarean sections (CS) are the most commonly performed surgical procedure worldwide, with 
approximately one-third of all births occurring via Caesarean section in developed nations,(1-3) 
and over of 40% of deliveries in some nation such as Brazil(4). Specifically in the United States of 
America, this equates to nearly 1.3 million deliveries in 2016(4, 5). Given the difficulties 
associated with women undergoing a CS, coupled with expectation of recovering from a large 
surgical procedure whilst caring for a newborn present new challenges to the mother and her 
family.  
 
Opioid analgesia is a common staple for post-surgical analgesia to aid in recovery. 
Unfortunately, due to the increase in Caesarean Section rates(1-3), there is more reliance on 
opioids to manage pain(6-9). This unfortunately is wrought with difficulties given the side-effect 
profile of opioid analgesics as well as their addictive potential(7). As a result, the reliance on 
alternative measures including surgical technique to minimise opioid requirements is an area of 
clinical research which requires further development(6, 9). 
 
Anaesthetic technique and post-operative pain management play an integral role in post-
operative pain. Another avenue which has been explored relates specifically to surgical 
techniques(2, 3, 5, 10-12). Studies have evaluated the type of incision(2, 3), method of skin 
closure(5), and closure of the peritoneum and its impact on post-operative pain(1). Specific to 
closure of the rectus fascia, Kahkhaie et al. evaluated the type of suture material used during 
Caesarean section and found their impact on post-operative pain(10). Finally, Trimbos et al. 
evaluated methods of fascial closure following midline laparotomy(12). Whilst these studies 
outline multiple surgical techniques and have shown impact on the risk of developing CPSP, no 
studies were found which directly compared the technique by which the fascia is reapproximated 
at the time of CS via a Pfannenstiel incision.   
 
The purpose of this protocol is to outline our study evaluating three methods of closure of the 
rectus fascia and their effect on post-operative pain in patients undergoing lower segment 
Caesarean sections (LSCS) via a Pfannenstiel incision in a Canadian tertiary care obstetrical unit. 
 
2 
STUDY RATIONALE 
 
LSCS are the most commonly performed surgical procedures worldwide. Given that much of the 
development of surgical approaches for trainees is based on the centre at which they are trained, 
there is no standardised approach which offers superiority as it relates to specific steps in the 
procedure. Given these issues, the notion of an evidence-based approach to fascial closure which 
minimises post-operative pain would be superior as it relates to the patient’s return to normal 
activities, duration of analgesia use and overall quality of life. It is for this reason we aim to 
undertake this study comparing three methods of rectus fascia closure during LSCS at our unit to 
ascertain if there is an impact on patient’s post-operative pain. 
 

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2.1 
Hypothesis 
Our study hypothesises that the presence of a thicker knot in the subcutaneous layer when 
closing the rectus fascia leads to more irritation of the cutaneous nerves causing more sensitivity 
and perceived pain by the patient. In addition, we also hypothesise that by burying the knot 
under the rectus fascia at the angle of the rectus incisions will further diminish the level of nerve 
irritation in the subcutaneous layer and will allow for a further reduction in perceived pain and 
analgesia requirements. 
 
3 
STUDY OBJECTIVES 
 
3.1 
Primary Objectives 
The primary objective in this study is to evaluate post-operative pain in patients undergoing 
elective lower segment caesarean sections via a Pfannenstiel incision. The intervention in 
question relates specifically to the method by which the rectus fascia is closed. Participants will 
fill in a pain questionnaire over a period of 10 weeks at set intervals to ascertain their level of 
pain on visual analogue scores and requirements for analgesia. 
 
3.2  
Secondary Objectives 
Our secondary objective relates specifically to whether there is a difference in pain in patients 
undergoing primary or repeat caesarean sections. This will also be determined using sub-group 
analysis of participant pain scores based upon their questionnaire responses. 
 
4 
STUDY DESIGN 
 
4.1 Study Overview 
The proposed study will be designed as a double-blinded, randomised, single-centre, clinical trial. 
Participants will be randomised into one of three groups based upon which method of rectus 
fascial closure will be undertaken. Post-operative questionnaires will be undertaken over a 10-
week period at set time points to elucidate post-operative pain. 
 
4.2 Strengths and Limitations 
The overall strength of this study lies in its randomisation of participants as a means of minimising 
bias. In addition, we aim to achieve a statistically significant result which can specifically target 
the efficacy of these three specific techniques in fascial closure and its impact on post-operative 
pain. As a result, this study will help to determine if a standardised method of fascial closure is 
more effective as it relates to post-operative pain when patients undergo a Pfannenstiel incision 
during their Caesarean section. 
 
With respect to limitations, this study only considers the use of a PolysorbTM absorbable sutures 
(CovidienTM) as the suture of choice in closure of the rectus fascia given this is the primary suture 
which is used in our unit. It does not consider the use of other suture materials including delayed 
absorbable monofilament sutures and their impact on post-operative pain. In addition, given the 
subjectivity of pain perception, we accept that this may impact our findings given participants 

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will have varying perceptions of their pain. We hope that by randomising our participants in each 
group, this will help to standardise our sample across all three groups. 
 
5 
SUBJECT SELECTION 
 
5.1 Study Population 
Our study population includes all women undergoing elective primary or repeat lower segment 
Caesarean sections via a Pfannenstiel incision at Sunnybrook Health Sciences Centre in Toronto, 
Canada. This is a tertiary care centre with approximately 4000 deliveries annually and a 
Caesarean section rate of 18%. The average rate of Caesarean sections in most developed 
countries is approximately one-third of all deliveries. 
 
5.2 Sample Size 
Our sample size is based upon a power of 80% at an alpha of 0.05 based on a two-sided t-test 
comparing groups. Based on these findings, our total sample size in each arm is 85 participants. 
In total, as there are three arms, our total sample size requires 255 participants, whereby 
randomising 85 participants to each group. In addition, we aim to undertake a sub-group analysis 
comparing primary to repeat Caesarean section with a power of 80% at an alpha of 0.05. Once 
again, a two-sided t-test would be used and based on these findings, we would require a total 
sample size of 140 participants, whereby comparing 70 participants per group. Given these 
minimum requirements and we estimate a drop-out rate of approximately 35%, we aim to recruit 
a total of 350 participants to this study. 
 
5.3 Inclusion Criteria 
 
1. Women aged 18-60 
2. Singleton pregnancies 
3. Patients undergoing elective LSCS via Pfannenstiel incision 
4. Use of regional anaesthesia (epidural, spinal anaesthesia, or combined spinal-epidural) 
 
5.4 Exclusion Criteria 
1. Multiple pregnancy 
2. Patient undergoing non-elective CS 
3. Caesarean section through midline laparotomy incision 
4. Patients undergoing CS under general anaesthsia 
5. History of chronic pain 
6. Post-operative complications (haematoma, abscess, dehiscence, re-operation) 
 
6 
PROPOSED INTERVENTION 
 
All participants will undergo a lower segment Caesarean section via a Pfannenstiel incision. All 
participants involved in this study will undergo some form of regional anaesthesia (epidural, 
spinal, or combined spinal and epidural anaesthesia). Participants requiring general anaesthesia 
will be excluded from this study. Subsequently, the procedure is carried out and the delivery of 

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the foetus is undertaken. The hysterotomy is closed and haemostasis is then ensured in the intra-
abdominal cavity. At our unit, the peritoneum is not re-approximated.  
 
Our proposed intervention involves three separate methods of closure of the rectus fascia which 
will be directly compared. Please refer to Appendix A to view diagrams outlining each method of 
fascial closure: 
 
1) The first method of fascial closure involves the use of one #1 PolysorbTM Polyglactin 910 
braided absorbable suture (CovidienTM). At one angle of the rectus fascia, both the 
anterior and posterior leafs are grasped using Bonney forceps and the suture is tied 
behind this angle. This suture is then used to re-approximate the fascia in a continuous 
fashion across the incision. Prior to completing the suturing of this layer, the contralateral 
side is grasped with a Kocher clamp to bring the fascia forward so that the suture can be 
tied to itself behind the contralateral incision. 
2) Method two involves two separate #1 PolysorbTM braided absorbable sutures 
(CovidienTM). Both leafs of the rectus fascia are grasped using the Bonney forceps and the 
suture is placed behind the angle of the incision above the rectus fascia. Subsequent to 
this, the rectus fascia is reapproximated in a continuous fashion until the suture reaches 
the contralateral rectus abdominus muscle. Subsequently, a second #1 PolysorbTM suture 
is tied behind the contralateral angle in the same fashion and the remainder of the rectus 
fascia is reapproximated in a continuous fashion until both sutures are met, whereupon 
they are tied together. 
3) The final method again involves two separate #1 PolysorbTM absorbable sutures 
(CovidienTM). Both leafs of the rectus fascia are grasped with the Bonney forceps and the 
suture is placed behind the angle of the incision ensuring that the entire knot of the suture 
is below the rectus fascia. Subsequent to this, the suture is run in a continuous fashion to 
reapproximate the fascia until reaching the contralateral rectus abdominus muscle. 
Subsequently, a second #1 PolysorbTM suture is tied behind the contralateral angle in the 
same fashion and the remainder of the rectus fascia is reapproximated in a continuous 
fashion until both sutures are met, whereupon they are tied together. 
 
The remainder of the procedure is completed whereupon the subcutaneous layer is inspected 
for haemostasis which is achieved using the electrocautery and is reapproximated if >2cm 
thickness with an absorbable suture. Subsequent to this, the skin is reapproximated using a 3-0 
Caprosyn® (polyglytone*6211) suture (CovidienTM) in a subcuticular fashion.  
 
As a means of enhancing analgesia, our centre utilises epidural morphine standard as part of their 
regional anaesthesia for Caesarean Sections, this utilises a single-dose of 0.15mg morphine for 
spinal regional anaesthesia or a single-dose of 3mg morphine for epidural regional anaesthesia. 
Upon completion of the procedure, the patient receives one dose of diclofenac 100mg per-
rectum and is initiated on oral analgesia as regional anaesthesia wears off. The patient receives 
a standard analgesia regimen including Tylenol 1g orally every 6 hours, Naproxen 500mg orally 
every 12 hours, and hydromorphone 1-2mg orally every 4 hours as required for breakthrough 

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pain. They are subsequently discharged home with a prescription of these three medications for 
a short course. 
 
 
7 
STUDY TREATMENTS 
 
7.1 Method of Assigning Subjects to Treatment Groups 
Up to 350 eligible patients will be randomly assigned to one of the three intervention groups in 
a 1:1 ratio using an Excel-based computer-generated randomisation scheme. 
 
7.2 Blinding 
Due to the objectives of the study, treatment group allocation will not be known to investigators, 
research staff, or patients. The operating surgeon will be informed which method of fascial 
closure will be undertaken. As such, these individuals will be excluded from collecting outcome 
data. Upon consenting to proceed with the study, Access to the randomisation code will be 
strictly controlled and the study blind will be broken on completion of the clinical study and after 
the study database has been locked. 
 
7.3 Data collection method 
Participants will be randomised to one of the three groups and will be provided a participant 
identification number on the day of their surgical procedure after consenting to proceed with the 
study. Subsequent to this, a chart review will be used to gather demographic information on 
participants, including age, gravida and para status, number of previous Caesarean sections, 
medical and surgical history, medication list, body mass index, and any obstetrical complications 
during the pregnancy. Participant’s e-mails will be collected and saved in a separate document 
to maintain confidentiality.  
 
Subsequent to this, participants will be e-mailed a link at each given time parameter to fill in their 
questionnaires which is a modified MD Anderson Brief Pain Inventory as a secure Google Docs 
Form (post-operative day #1 and 2, and at 2, 6 and 10 weeks post-operatively). As the 
participant’s only identification is their participant identification number, this maintains 
participant confidentiality.  
 
8 
WITHDRAWAL OF SUBJECTS FROM THE STUDY 
 
A subject may be withdrawn from the study at any time if the subject, the investigator, or the 
Sponsor feels that it is not in the subject’s best interest to continue. 
 
All subjects are free to withdraw from participation at any time, for any reason, specified or 
unspecified, and without prejudice. 
 

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Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals. The reason for the subject’s withdrawal from the study will be specified in the 
subject’s source documents. 
 
Subjects who withdraw from the study will not be replaced. 
 
9 
DATA SAFETY MONITORING 
 
Sunnybrook Health Sciences Centre Data Safety Monitoring Board (DSMB) will establish a Data 
Monitoring Committee (DMC) to review data related to safety and efficacy, to ensure scientific 
validity and merit of the study, according to Sunnybrook Health Sciences Centre Data Safety 
Monitoring Board Operations Manual and a DMC Charter to be established for this protocol.  
 
10 
STATISTICAL METHODS AND CONSIDERATIONS 
 
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will be written 
describing all analyses that will be performed. The SAP will contain any modifications to the 
analysis plan described below. 
 
10.1 Demographic and Baseline Characteristics 
The following demographic variables will be collected through a chart review: age, gravida and 
para status, total number of previous CS, medical history, surgical history, ethnicity, obstetrical 
history, current obstetrical complications in this pregnancy, medications, height, and weight. 
 
10.2 Statistical Analysis 
For our primary outcome measure, we aim to perform statistical analysis using IBM® SPSS® 
Version. 26 Statistics Software for Windows to perform a two-sided T-test whereby comparing 
groups directly. Based upon an 80% power at an alpha of 0.05, we anticipate a 15% when 
comparing group 1 vs 2 and group 1 vs 3, we require a sample size of 255 participants across all 
three groups. 
 
Specific to our subgroup analysis evaluating primary vs. repeat caesarean section, based upon an 
80% power at an alpha of 0.05, we anticipate a 15% difference in comparing these two groups 
using a two-sided T-test. As a result, we require a sample size of 140 participants across these 
two groups. 
 
11 
DATA COLLECTION, RETENTION AND MONITORING 
 
11.1 
Data Collection Instruments 
The Investigator will prepare and maintain adequate and accurate source documents designed 
to record all observations and other pertinent data for each subject treated with the study drug. 
 

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Study personnel will enter data from source documents corresponding to a subject’s visit into 
the protocol-specific electronic Case Report Form (eCRF) OR paper CRF when the information 
corresponding to that visit is available.  Subjects will not be identified by name in the study 
database or on any study documents to be collected by the research team, but will be identified 
by a participant identification number. 
 
For eCRFs: If a correction is required for an eCRF, the time and date stamps track the person 
entering or updating eCRF data and creates an electronic audit trail.  For paper CRFs:  If a 
correction is made on a CRF, the study staff member will line through the incorrect data, write in 
the correct data and initial and date the change. 
 
The Investigator is responsible for all information collected on subjects enrolled in this study.  All 
data collected during the course of this study must be reviewed and verified for completeness 
and accuracy by the Investigator.  A copy of the CRF will remain at the Investigator’s site at the 
completion of the study. 
 
11.2 
Data Management Procedures 
The data will be entered into a validated database.  The Data Management group will be 
responsible for data processing, in accordance with procedural documentation.  Database lock 
will occur once quality assurance procedures have been completed. 
 
All procedures for the handling and analysis of data will be conducted using good computing 
practices meeting FDA guidelines for the handling and analysis of data for clinical trials. 
 
11.3 
Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data validation 
checks will be implemented and applied to the database on a regular basis. The study database 
will be updated in accordance with the resolved queries. All changes to the study database will 
be documented. 
 
11.4 
Archival of Data 
The database is safeguarded against unauthorized access by established security procedures; 
appropriate backup copies of the database and related software files will be 
maintained.  Databases are backed up by the database administrator in conjunction with any 
updates or changes to the database.   
 
At critical junctures of the protocol (e.g., production of interim reports and final reports), data 
for analysis is locked and cleaned per established procedures. 
 
11.5 
Availability and Retention of Investigational Records 
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Sponsor (or designee), IRB/IEC, and Regulatory Agency (e.g., FDA) 
inspectors upon request.  A file for each subject must be maintained that includes the signed 
Informed Consent, HIPAA Authorization and Assent Form and copies of all source documentation 

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related to that subject.  The Investigator must ensure the reliability and availability of source 
documents from which the information on the CRF was derived. 
 
All study documents (patient files, signed informed consent forms, copies of CRFs, Study File 
Notebook, etc.) must be kept secured for a period of seven years following completion of the 
study.  There may be other circumstances for which the Sponsor is required to maintain study 
records and, therefore, the Sponsor should be contacted prior to removing study records for any 
reason. 
 
11.6 
Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to the U.S. CFR 
Title 21 Parts 50, 56, and 312 and ICH Guidelines for GCP (E6).    By signing this protocol, the 
Investigator grants permission to the Sponsor (or designee), and appropriate regulatory 
authorities to conduct on-site monitoring and/or auditing of all appropriate study 
documentation. 
 
11.7 
Subject Confidentiality 
In order to maintain subject confidentiality, only the participant identification number will 
identify all study subjects on CRFs and other documentation submitted to the Sponsor. Additional 
subject confidentiality issues (if applicable) are covered in the Clinical Study Agreement. 
 
12 
ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
 
The study will be conducted according to the Declaration of Helsinki, Protection of Human 
Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and Obligations of Clinical 
Investigators (21 CFR 312). 
 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other records 
will be identified by a coded number and initials only.  All study records will be kept in a locked 
file cabinet and code sheets linking a patient’s name to a patient identification number will be 
stored separately in another locked file cabinet.  Clinical information will not be released without 
written permission of the subject, except as necessary for monitoring by the FDA.  The 
Investigator must also comply with all applicable privacy regulations (e.g., Health Insurance 
Portability and Accountability Act of 1996, EU Data Protection Directive 95/46/EC). 
 
12.1 Protocol Amendments 
Any amendment to the protocol will be written by the research team. Protocol amendments 
cannot be implemented without prior written IRB/IEC approval except as necessary to eliminate 
immediate safety hazards to patients. A protocol amendment intended to eliminate an apparent 
immediate hazard to patients may be implemented immediately, provided the IRBs are notified. 
 
12.2 Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB/IEC of each 
participating center prior to study initiation.  Serious adverse experiences regardless of causality 

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will be reported to the IRB/IEC in accordance with the standard operating procedures and policies 
of the IRB/IEC, and the Investigator will keep the IRB/IEC informed as to the progress of the study.  
The Investigator will obtain assurance of IRB/IEC compliance with regulations. 
 
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, protocol 
amendments, Investigator’s Brochure, consent forms, information concerning patient 
recruitment, payment or compensation procedures, or other pertinent information) will be 
submitted to the IRB/IEC.  The IRB/IECs written unconditional approval of the study protocol and 
the informed consent form will be in the possession of the Investigator before the study is 
initiated.  The IRB/IECs unconditional approval statement will be transmitted to the Research 
Team prior to initiation of this study.  This approval must refer to the study by exact protocol title 
and number and should identify the documents reviewed and the date of review. 
 
Protocol and/or informed consent modifications or changes may not be initiated without prior 
written IRB/IEC approval except when necessary to eliminate immediate hazards to the patients 
or when the change(s) involves only logistical or administrative aspects of the study.  Such 
modifications will be submitted to the IRB/IEC and written verification that the modification was 
submitted and subsequently approved should be obtained.   
 
The IRB/IEC must be informed of revisions to other documents originally submitted for review; 
serious and/or unexpected adverse experiences occurring during the study in accordance with 
the standard operating procedures and policies of the IRB; new information that may affect 
adversely the safety of the patients of the conduct of the study; an annual update and/or request 
for re-approval; and when the study has been completed. 
 
12.3 Informed Consent Form 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH GCP, US 
Code of Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a,b], CFR 50.27, and 
CFR Part 56, Subpart A), the Health Insurance Portability and Accountability Act (HIPAA, if 
applicable), and local regulations. 
 
The Investigator will prepare the informed consent form, assent and HIPAA authorization and 
provide the documents to the Sponsor or designee for approval prior to submission to the 
IRB/IEC.  The consent form generated by the Investigator must be acceptable to the Sponsor and 
be approved by the IRB/IEC.  The written consent document will embody the elements of 
informed consent as described in the International Conference on Harmonisation and will also 
comply with local regulations. The Investigator will send an IRB/IEC-approved copy of the 
Informed Consent Form to the Sponsor (or designee) for the study file. 
 
A properly executed, written, informed consent will be obtained from each subject prior to 
entering the subject into the trial.  Information should be given in both oral and written form and 
subjects (or their legal representatives) must be given ample opportunity to inquire about details 
of the study.  If appropriate and required by the local IRB/IEC, assent from the subject will also 
be obtained.  If a subject is unable to sign the informed consent form (ICF) and the HIPAA 

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authorization, a legal representative may sign for the subject.   A copy of the signed consent form 
(and assent) will be given to the subject or legal representative of the subject and the original will 
be maintained with the subject’s records. 
 
12.4 Publications 
The preparation and submittal for publication of manuscripts containing the study results shall 
be in accordance with a process determined by mutual written agreement among the study 
Sponsor and participating institutions.  The publication or presentation of any study results shall 
comply with all applicable privacy laws, including, but not limited to, the Health Insurance 
Portability and Accountability Act of 1996.  
 
12.5 Investigator Responsibilities 
By being involved in this study, the Investigators, as part of the Research Team, agrees to: 
1. Conduct the study in accordance with the protocol and only make changes after notifying 
the Sponsor (or designee), except when to protect the safety, rights or welfare of subjects. 
2. Personally conduct or supervise the study (or investigation). 
3. Ensure that the requirements relating to obtaining informed consent and IRB review and 
approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. Report to the Sponsor or designee any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64. 
5. Ensure that all associates, colleagues and employees assisting in the conduct of the study 
are informed about their obligations in meeting the above commitments. 
6. Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make 
those records available for inspection with the Sponsor (or designee). 
7. Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be responsible 
for initial and continuing review and approval of the clinical study. 
8. Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity 
and all unanticipated problems involving risks to subjects or others. 
9. Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators and all 
other pertinent requirements listed in § 21 CFR part 312. 
 
 
 
 
 
 
 
 
 
 
 
 

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REFERENCES 
 
1. 
Tabasi Z, Mahdian M, Abedzadeh-Kalahroudi M. Closure or non-closure of peritoneum in 
cesarean section: outcomes of short-term complications. Arch Trauma Res. 2013;1(4):176-9. 
2. 
Vejnović TR, Costa SD, Ignatov A. New Technique for Caesarean Section. Geburtshilfe 
Frauenheilkd. 2012;72(9):840-5. 
3. 
AbdElaal NK, Ellakwa HE, Elhalaby AF, Shaheen AE, Aish AH. Scalpel versus diathermy skin 
incision in Caesarean section. J Obstet Gynaecol. 2019;39(3):340-4. 
4. 
Sun KW, Pan PH. Persistent pain after cesarean delivery. Int J Obstet Anesth. 2019;40:78-90. 
5. 
Mackeen AD, Khalifeh A, Fleisher J, Han C, Leiby B, Berghella V. Pain Associated With Cesarean 
Delivery Skin Closure: A Randomized Controlled Trial. Obstet Gynecol. 2015;126(4):702-7. 
6. 
Sutton CD, Carvalho B. Optimal Pain Management After Cesarean Delivery. Anesthesiol Clin. 
2017;35(1):107-24. 
7. 
Landau R. Post-cesarean delivery pain. Management of the opioid-dependent patient before, 
during and after cesarean delivery. Int J Obstet Anesth. 2019;39:105-16. 
8. 
Schyns-van den Berg AM, Huisjes A, Stolker RJ. Postcaesarean section analgesia: are opioids still 
required? Curr Opin Anaesthesiol. 2015;28(3):267-74. 
9. 
Carvalho B, Butwick AJ. Postcesarean delivery analgesia. Best Pract Res Clin Anaesthesiol. 
2017;31(1):69-79. 
10. 
Rezaie Kahkhaie K, Rezaie Keikhaie K, Shahreki Vahed A, Shirazi M, Amjadi N. Randomized 
comparison of nylon versus absorbing polyglactin 910 for fascial closure in caesarean section. Iran Red 
Crescent Med J. 2014;16(4):e12580. 
11. 
Rafique Z, Shibli KU, Russell IF, Lindow SW. A randomised controlled trial of the closure or non-
closure of peritoneum at caesarean section: effect on post-operative pain. Bjog. 2002;109(6):694-8. 
12. 
Trimbos JB, Smit IB, Holm JP, Hermans J. A randomized clinical trial comparing two methods of 
fascia closure following midline laparotomy. Arch Surg. 1992;127(10):1232-4. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX A: Informed Consent Form 
 

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APPENDIX B: Figures Showing Methods of Fascial Closure 
 

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APPENDIX C: Pain Survey Questionnaire 
Fascial Closure – Follow-up Study Questionnaire: 
 
Your personal ID: ____________________ 
 
Throughout our lives, most of us have had pain from time to time (such as minor headaches, sprains, 
and toothaches). Have you had pain other than these everyday kinds of pain today? 
□ 
Yes 
□ 
No 
 
Did you take pain medication in the last 7 days? 
□ 
Yes 
□ 
No 
 
I feel I have some form of pain now that requires medication each and every day. 
□ 
Yes 
□ 
No 
 
If your answers to the above 3 questions were all “No”, please stop here and go to the end of the 
questionnaire and please press “Submit”. If any of the above 3 answers were “Yes”, please continue. 
 
On the diagram below, please identify the area that hurts the most. 
 
□ 
A 
□ 
B 
□ 
C 
□ 
D 
□ 
E 
□ 
F 
□ 
G 
□ 
H 
□ 
I 
□ 
J 
□ 
K 
□ 
L 
□ 
M 
□ 
N 
 
Where would you identify this pain? 
□ 
Superficial (closer to the skin) 
 
□ 
Deep 
 
Please rate the number that describes your pain level at its WORST in the last 24 hours 
 
0     1     2     3     4     5     6     7     8     9     10 

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No Pin □     □    □     □    □     □     □    □     □    □      □ 
Worst pain you can imagine 
 
Please rate the number that describes your pain level at its LEAST in the last 24 hours. 
 
0     1     2     3     4     5     6     7     8     9     10 
No Pin □     □    □     □    □     □     □    □     □    □      □ 
Worst pain you can imagine 
 
Please rate the number that describes your pain level on AVERAGE. 
 
0     1     2     3     4     5     6     7     8     9     10 
No Pin □     □    □     □    □     □     □    □     □    □      □ 
Worst pain you can imagine 
 
Please rate the number that describes your pain level RIGHT NOW. 
 
0     1     2     3     4     5     6     7     8     9     10 
No Pin □     □    □     □    □     □     □    □     □    □      □ 
Worst pain you can imagine 
 
What kind of things make your pain feel better? (i.e. heat, medicine, rest, massage)? 
__________________________________________________ 
 
What kinds of things make your pain worse (i.e. walking, standing, lifting)? 
__________________________________________________ 
 
What treatments or medications are you receiving for pain? 
__________________________________________________ 
 
In the last 24 hours, how much relief have pain treatments or medications provided? Please identify the 
percentage that shows how much relief you have received. 
0%   10%    20%     30%    40%    50%     60%    70%    80%    90%    100% 
No Relief 
 □       □         □          □         □         □          □         □         □         □          □ 
Complete relief      
 
For each of the following words, please check all adjectives that apply to your pain. 
□ 
Aching 
□ 
Burning 
□ 
Dull 
□ 
Exhausting 
□ 
Gnawing 
□ 
Miserable 
□ 
Nagging 
□ 
Numb 
□ 
Penetrating 
□ 
Pulling 
□ 
Sharp 
□ 
Shocking 
□ 
Shooting 
□ 
Stabbing 
□ 
Tender 

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□ 
Throbbing 
□ 
Tiring 
□ 
Unbearable 
 
In the last 24 hours, how much has your pain interfered with your general activity? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your mood? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your walking ability? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your normal work (includes both work 
outside the home and housework)? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your relations with other people? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your sleep? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
In the last 24 hours, how much has your pain interfered with your enjoyment of life? 
 
 
 
0     1     2     3     4     5     6     7     8     9     10 
Does not interfere 
□     □    □     □    □     □     □    □     □    □      □ 
Completely interferes 
 
I prefer to take my pain medication: 
□ 
On a regular basis 
□ 
Only when necessary 
□ 
Do not take pain medicine 
 
I take my pain medicine (in a 24 hour period): 
□ 
Not every day 
□ 
1 to 2 times per day 
□ 
3 to 4 times per day 
□ 
5 to 6 times per day 
□ 
more than 6 times per day 

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Do you feel you need a stronger type of pain medication? 
□ 
Yes 
□ 
No 
□ 
Uncertain 
 
Other methods I use to relieve my pain include: (Please check all that apply) 
□ 
Warm compresses 
□ 
Cold compresses 
□ 
Relaxation techniques 
□ 
Distraction 
□ 
Biofeedback 
□ 
Hypnosis 
□ 
Other: ________________________