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
Organisation
Erasmus Medical University Rotterdam
Sponsor details
Wytemaweg 80
Rotterdam
3015 CN
Netherlands
Sponsor type
Hospital/treatment centre
Website
Organisation
Universitaire Ziekenhuizen Leuven
Sponsor details
Sponsor type
Not defined
Website
Funders
Funder type
Industry
Funder name
Medtronic
Alternative name(s)
Medtronic Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
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