Prospective controlled randomised trial on Prevention Of Postoperative abdominal Adhesions by icodextrin 4% solution after laparotomic operation for small bowel obstruction caused by adherences

ISRCTN	ISRCTN22061989
DOI	https://doi.org/10.1186/ISRCTN22061989
Secondary identifying numbers	001

Submission date: 17/12/2006
Registration date: 05/07/2007
Last edited: 27/10/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Fausto Catena
Scientific

Via Lidice 4
Bologna
40139
Italy

Email	fcatena@aosp.bo.it

Study information

Study design	Prospective randomized controlled investigation
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Prospective controlled randomised trial on Prevention Of Postoperative abdominal Adhesions by icodextrin 4% solution after laparotomic operation for small bowel obstruction caused by adherences
Study acronym	POPA study: Prevention of Postoperative Adhesions
Study objectives	Adhesive Small Intestine Occlusions (ASIO) are an important cause of hospital admission and are associated with significant morbidity and mortality, placing a substantial burden on healthcare systems worldwide. Postoperative adhesions account for more than 40% of all cases of intestinal obstruction, with 60 to 70% of those involving the small bowel. Of patients who require abdominal reoperation, 30 to 44% have adhesion-related intestinal obstruction. For small-bowel obstruction, the incidence rises to 65 to 75%. Mortality rates range from 3% for simple intestinal obstructions to 30% when the bowel becomes necrotic or perforated. The cumulative recurrence rate for patients operated once for ASIO is 18% after ten years and 29% at 30 years. For patients admitted several times for ASIO, the relative risk of recurrent ASIO increases with the increasing number of prior ASIO episodes. The cumulative recurrence rate reaches 81% for patients with four or more ASIO admissions. In USA adhesiolysis is responsible for more than 300,000 hospitalisations annually, accounting for nearly 850,000 days of inpatient care and $1.3 billion in hospitalisation and surgical expenditures. An increasing number of adhesion-reduction agents, in the form of site-specific and broad-coverage barriers and solutions, are becoming available to surgical teams to complement optimal surgical techniques. Icodextrin 4% solution (Adept, Shire Pharmaceuticals, UK) is a high-molecular-weight a-1,4 glucose polymer that is approved in Europe for use as an intra-operative lavage and a post-operative instillate to reduce the occurrence of post-surgery intra-abdominal adhesions. The icodextrin colloid is absorbed slowly, resulting in the retention of the fluid within the peritoneal cavity for more than four days. The solution reduces adhesions by a process of hydroflotation, keeping the peritoneal organs and tissues apart during the critical post-surgery period when the patient is at greatest risk of adhesion formation. Icodextrin has an extensive safety profile and has been used as a 7.5% solution in Continuous Ambulatory Peritoneal Dialysis (CAPD) for more than 50,000 patient-years. In addition, preclinical and preliminary clinical studies have demonstrated the safety and efficacy of icodextrin 4% solution in the reduction of adhesion formation following abdomino-pelvic surgery. In literature there are no randomised trials on the use of this solution to prevent adhesions after ASIO operation. The current clinical study evaluates the safety and effectiveness of icodextrin 4% for decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASIO.
Ethics approval(s)	Approval received from the Ethics Board of St Orsola Malpighi University Hospital on the 11/12/2006, ref: 112/2006/U/ disp
Health condition(s) or problem(s) studied	Prevention of postoperative abdominal adhesions
Intervention	The study will be performed in the Department of Transplant, General and Emergency Surgery of St Orsola-Malpighi University Hospital (Bologna, Italy); a large teaching institution, with the participation of all surgeons who accept to be involved, together with the Emergency Surgery Department of Maggiore Hospital (Bologna, Italy). These two institutions serve all surgical emergencies of Bologna city. The study is designed and conducted in compliance with the principles of Good Clinical Practice regulations. ASIO is a common disease. Any improvement in this field will benefit many patients reducing the re-operative rate. All our patients will be informed about the study and an informed consent will be obtained. There will be no inconvenience caused to the patients. All of the medical information obtained from the patients will be kept confidentially among the research scientists conducting the study. The patients will be free to withdraw from the study whenever they want without any obligation. Preoperative data collected includes patient demographics and co-morbid conditions (genitourinary, cardiac, pulmonary, gastrointestinal, renal, or rheumatological) and a detailed history of previous occlusions and surgical procedures. A decompression with nasogastric tube is carried out. The average nasogastric tube output of each patient (total amount of drainage/duration) is calculated. For patients submitted to Gastrografin administration before surgery only the output before the procedure is considered. Intravenous fluid therapy is performed. Plain abdomen X-rays are done and maximal small intestine diameter is calculated. The duration of symptoms before admission and the number of previous operations are also evaluated. Subjects with surgical indication to laparotomy are enrolled and randomised. A written informed consent is obtained. The laparotomic surgical procedure is carried out and existing abdominal cavity adhesions are documented. Subjects are submitted to adhesiolysis with bowel resection if necessary with or without anastomosis. The first group receive traditional treatment (control group) whereas the second group is treated with icodextrin 4% before abdomen closure. The use of irrigants during surgery is not allowed. Peritoneal contamination is evaluated with cultures. Per protocol the abdominal fascia is closed with a running Polydioxone Suture (PDS) and the skin is closed with sutures or skin staples. Only one abdominal drainage is allowed in case of bowel resection and it has to be removed seven days after the operation. In case of bowel leakage the patient will drop out from the study. For all patients, perioperative parameters are recorded, including blood loss, total length of the midline incision, method of anastomosis, method and timing of incision openings and closures, corticosteroid use. Operative wounds are classified as clean, clean contaminated, and contaminated as described by Schwartz et. al. The patients are followed-up for five years. In case of reoperation for ASIO the procedure is carried out by a third party blinded to the patients previous anti-adhesive treatment: this surgeon evaluates incidence, location, severity, and extent of adhesions. The incidence of adhesions is assigned a severity score of: 0: no adhesions 1: filmy thickness, avascular 2: moderate thickness, limited vascularity, or 3: dense thickness, vascularised Adverse Events (AEs) are collected for the duration of the study, beginning at the time of randomisation. AEs are identified and described by the primary investigators.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Icodextrin
Primary outcome measure	To evaluate the therapeutic role of icodextrin 4% to reduce ASIO incidence.
Secondary outcome measures	To reduce adherences rate (in case of reoperation for ASIO).
Overall study start date	01/01/2007
Completion date	01/01/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	180
Total final enrolment	91
Key inclusion criteria	1. Adult patients (over 18 years) 2. Submitted to laparotomic surgical procedures for ASIO 3. Clinical and radiological evidence of adhesive small intestine obstruction 4. American Society of Anesthesiologists (ASA) grade one to three patients 5. Informed consent
Key exclusion criteria	1. Intra-abdominal cancer 2. Peritoneal contamination 3. Inflammatory Bowel Disease (IBD) 4. Positive history of radiotherapy 5. Patients with an intra-operative findings of different pathology will be excluded from the study
Date of first enrolment	01/01/2007
Date of final enrolment	01/01/2009

Locations

Countries of recruitment

Italy

Study participating centre

Via Lidice 4

Bologna
40139
Italy

Sponsor information

Baxter Biosurgery (Italy)
Industry

c/o Laura Caliari
Viale Tiziano, 25
Rome
00196
Italy

Email	laura_caliari@baxter.com
Website	http://www.baxter.com
"ROR"	https://ror.org/02kf9ya90

Funders

Funder type

Hospital/treatment centre

St Orsola Malpighi University Hospital Bologna (Italy)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	18/12/2008	06/01/2021	Yes	No
Results article		01/02/2012	27/10/2021	Yes	No

Editorial Notes

27/10/2021: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
06/01/2021: Publication reference added.