Biomarkers for colorectal anastomotic leakage
| ISRCTN | ISRCTN84052649 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN84052649 |
| Secondary identifying numbers | NL52251.078.15 |
- Submission date
- 04/10/2018
- Registration date
- 23/10/2018
- Last edited
- 31/03/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Plain English summary of protocol
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
Contact information
Public
Wytemaweg 80
Rotterdam
3015 CN
Netherlands
 ORCID ID |
0000-0002-4606-6895 |
|---|
Study information
| Study design | International prospective multicenter cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Scientific title | Analysis of predictive parameters for evident anastomotic leakage - II |
| Study acronym | APPEAL-II |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/01/2015 |
| Completion date | 01/10/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 300 |
| Total final enrolment | 271 |
| Key inclusion criteria | Patients who underwent partial mesorectal excision (PME) or total mesorectal excision (TME) with construction of a colorectal anastomosis |
| Key exclusion criteria | 1. Pregnancy 2. Age < 18 years 3. No informed consent 4. No drain 5. Emergency surgery |
| Date of first enrolment | 01/08/2015 |
| Date of final enrolment | 31/10/2017 |
Locations
Countries of recruitment
- Belgium
- Netherlands
Study participating centres
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Netherlands
Sponsor information
Hospital/treatment centre
Herestraat 49
Leuven
3000
Belgium
| Website | https://www.uzleuven.be/en |
|---|---|
"ROR" |
https://ror.org/0424bsv16 |
Hospital/treatment centre
Wytemaweg 80
Rotterdam
3015 CN
Netherlands
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Medtronic Inc.
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/10/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal. |
| IPD sharing plan | 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 07/11/2021 | 31/03/2022 | Yes | No |
Editorial Notes
31/03/2022: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
