Condition category
Surgery
Date applied
04/10/2018
Date assigned
23/10/2018
Last edited
23/10/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The most important and frustrating complication of rectal surgery is anastomotic leakage. This is when a defect causes the contents of the colon (bowel) to leak into the abdominal and/or pelvic space, leading to peritonitis (infection), abscess (collection of pus) and sepsis that can be fatal. The incidence varies between 3% and 19% and mortality (death) rates vary between 10% and 20%. Anastomotic leakage is a severe complication which prolongs hospital stay by one to two weeks and increases medical costs by as much as $24,000, triple the cost compared to normal recovery. The occurrence of this complication is poorly understood. Fever, abdominal pain and impaired gastrointestinal transit are signs of anastomotic leakage but these are common after rectal surgery and not specific for leakage. Anastomotic leakage is usually detected between day 5 and day 8 after surgery. Early diagnosis is necessary as delayed diagnosis of anastomotic leakage increases mortality. A delay in diagnosis of 2.5 days increases mortality from 24% to 39%. In most cases, CT scanning is required to confirm anastomotic leakage, but with this technique it is impossible to detect anastomotic leakage in at early stage. Therefore, this study aims to find a biomarker in blood or drain fluid to early detect anastomotic leakage after rectal resection (surgery).

Who can participate?
Patients aged over 18 who underwent partial or total mesorectal excision (removal of a significant length of the bowel) with construction of a colorectal anastomosis (cross-connection)

What does the study involve?
All patients receive a pelvic drain during surgery which is kept in place for at least three days after surgery. Drain fluid is collected every morning on the first three days. The drain fluid reservoir is replaced after drain fluid collection. Drain fluid is analysed in batch after including all patients. In addition, C-reactive protein (CRP) is measured in blood samples on the first three days.

What are the possible benefits and risks of participating?
There are no benefits for the participating patients nor will their hospitalization be prolonged. On the other hand there are risks related to the participation of this study. These risks are due to the placement of a drain during colorectal surgery and due to the collection of blood samples. Despite the fact that a drain is widely used in colorectal surgery, the placement of a drain could cause wound infection. However, the rates of wound infection with and without a drain are similar.

Where is the study run from?
This study is a collaboration between UZ Leuven, Belgium and Erasmus MC Rotterdam, the Netherlands. In total, ten hospitals participated in this study

When is the study starting and how long is it expected to run for?
January 2015 to October 2019

Who is funding the study?
Medtronic

Who is the main contact?
C.L. Sparreboom

Trial website

Contact information

Type

Public

Primary contact

Ms Cloe Sparreboom

ORCID ID

http://orcid.org/0000-0002-4606-6895

Contact details

Wytemaweg 80
Rotterdam
3015 CN
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NL52251.078.15

Study information

Scientific title

Analysis of predictive parameters for evident anastomotic leakage - II

Acronym

APPEAL-II

Study hypothesis

This study aimed to find systemic and peritoneal biomarkers for anastomotic leakage after rectal resection. This study will explore combinations of biomarkers as a clinically useful diagnostic tool for early detection of anastomotic leakage after rectal resection.

Ethics approval

1. Belgium: Committee Medical Ethics UZ KU Leuven, 17/07/2015, ref: B322201525195
2. The Netherlands: The Medical Ethical Committee of Erasmus University Medical Center, 24/11/2015m ref: NL52251.078.15

Study design

International prospective multicenter cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Condition

Anastomotic leakage after rectal resection

Intervention

All patients received a pelvic drain during surgery which will kept in place for at least 3 postoperative days. Drain fluid was collected every morning on the first three postoperative days respecting rules of sterility. The drain fluid reservoir was replaced after drain fluid collection. Drain fluid stored in a -80°C fridge and analysed in batch after including all patients. In addition, C-reactive protein (CRP) was measured in peripheral blood samples on the first three postoperative days according to the hospitals’ protocol. Follow-up ended at the first outpatient clinic visit after discharge.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Colorectal anastomotic leakage was defined as a clinically manifest insufficiency of the anastomosis, leading to a clinical state requiring treatment. It was confirmed by either endoscopy, CT-scan and/or contrast enema or reoperation. Treatment consisted of therapeutic antibiotics, drainage or a surgical re-intervention. The primary endpoint does not occur at a specific time point since it involves a postoperative complication. Follow-up ends at the first outpatient clinic visit after discharge.

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/01/2015

Overall trial end date

01/10/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Patients who underwent partial mesorectal excision (PME) or total mesorectal excision (TME) with construction of a colorectal anastomosis

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. Pregnancy
2. Age < 18 years
3. No informed consent
4. No drain
5. Emergency surgery

Recruitment start date

01/08/2015

Recruitment end date

31/10/2017

Locations

Countries of recruitment

Belgium, Netherlands

Trial participating centre

Havenziekenhuis
3011 TD
Netherlands

Trial participating centre

IJsselland Ziekenhuis
2906 ZC
Netherlands

Trial participating centre

Reinier de Graaf Gasthuis
2625 AD
Netherlands

Trial participating centre

Isala Ziekenhuis
8025 AB
Netherlands

Trial participating centre

VU University Medical Center
1081 HV
Netherlands

Trial participating centre

University Medical Center Utrecht
3584 CX
Netherlands

Trial participating centre

Jeroen Bosch Ziekenhuis
5223 GZ
Netherlands

Trial participating centre

OLVG
1091 AC
Netherlands

Trial participating centre

University Hospital Leuven
3000
Netherlands

Trial participating centre

University Hospital Antwerpen
2650
Netherlands

Sponsor information

Organisation

University Hospital Leuven

Sponsor details

Herestraat 49
Leuven
3000
Belgium

Sponsor type

Hospital/treatment centre

Website

https://www.uzleuven.be/en

Organisation

Erasmus Medical University Rotterdam

Sponsor details

Wytemaweg 80
Rotterdam
3015 CN
Netherlands

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Industry

Funder name

Medtronic

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal.

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available due to the fact that no ethical approval was obtained to publish the dataset.

Intention to publish date

01/10/2019

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes