Condition category
Surgery
Date applied
17/12/2006
Date assigned
05/07/2007
Last edited
05/07/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Fausto Catena

ORCID ID

Contact details

Via Lidice 4
Bologna
40139
Italy
fcatena@aosp.bo.it

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

001

Study information

Scientific title

Acronym

POPA study: Prevention of Postoperative Adhesions

Study hypothesis

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

Approval received from the Ethics Board of St Orsola Malpighi University Hospital on the 11th December 2006 (ref: 112/2006/U/ disp).

Study design

The study project is a prospective, randomised controlled investigation

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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 patient’s 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

Phase

Not Specified

Drug names

Icodextrin

Primary outcome measures

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 trial start date

01/01/2007

Overall trial end date

01/01/2009

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

180

Participant 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

Recruitment start date

01/01/2007

Recruitment end date

01/01/2009

Locations

Countries of recruitment

Italy

Trial participating centre

Via Lidice 4
Bologna
40139
Italy

Sponsor information

Organisation

Baxter Biosurgery (Italy)

Sponsor details

c/o Laura Caliari
Viale Tiziano
25
Rome
00196
Italy
laura_caliari@baxter.com

Sponsor type

Industry

Website

http://www.baxter.com

Funders

Funder type

Hospital/treatment centre

Funder name

St Orsola Malpighi University Hospital Bologna (Italy)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes