Remote Ischemic Preconditioning (RIPC) versus sham-control for reduction of Anastomotic Leakage after resection for rectal cancer: a prospective, randomized controlled, triple-blind, clinical phase III monocenter trial
Organizational Data
- DRKS-ID:
- DRKS00018942
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2019-10-31
- Last update in DRKS:
- 2022-09-28
- Registration type:
- Prospective
Acronym/abbreviation of the study
RIPAL
URL of the study
http://keine Internetseite vorhanden
Brief summary in lay language
Anastomotic leakage (= suture leaking) is a dreaded complication after surgery on the rectum. This often occurs due to ischemia (= reduced blood supply) of the anastomotic region. There is still an urgent need for methods to prevent suture leaks, which can be devastating, causing septicemia, reoperation, or even the death of the patient. "Remote ischemic preconditioning" (RIPC) is a novel approach in which a short amount of hypoperfusion is given away from the target organ (e.g., intestine or liver) e.g. by inflating a blood pressure cuff on an arm for 5 minutes. As a result, bodily substances, which mediate a complex control loop that protects against damage from reduced blood flow to the target organ. Numerous studies have demonstrated this protective effect for RIPC in various organs (e.g., brain, heart, kidney, liver). The planned study is the first study and the first pilot RCT (randomized controlled trial) that will investigate whether RIPC reduces the rate of anastomotic leakage after resection for rectal cancer compared to the control intervention (= sham-RIPC). During the 30-day follow-up period, the following outcomes will be assessed: surgical complications, reinterventions, hospital stay, readmission. A positive study outcome would be of high patient and clinical relevance due to the serious effects of anastomotic leakage.
Brief summary in scientific language
"Remote ischemic preconditioning" (RIPC) is an innovative approach that differs from other preconditioning strategies in that the ischemic stimulus (by inflating a blood pressure cuff on one extremity) is performed remotely from the target organ. As a result, several cytokines, are released, which protect the target organ against ischemic damage via a complex control loop. RIPC induces the release of serotonin from platelets, which stimulates VEGF secretion, which in turn up-regulates the release of IL10 and Mmp8 in the target organs. There are already multiple studies demonstrating that RIPC attenuates ischemia-reperfusion injury in various organ systems. Gastrointestinal anastomoses are highly vulnerable to ischemic injury and therefore anastomotic leakage has often an ischemic genesis. To what extent RIPC after rectal resection has a protective effect on the development of anastomotic leakage is still unclear.
Health condition or problem studied
- ICD10:
- C20 - Malignant neoplasm of rectum
- ICD10:
- K91.83
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- Experimental Arm/ Study Intervention: In RIPC, a blood pressure cuff is placed around an arm immediately prior to surgery (after induction of anesthesia and before/ during incision/dissection) and inflated to 200 mmHg or a pressure ≥50 mmHg above systolic pressure for 5 minutes (= limb ischemia). This corresponds to the ischemic stimulus distant from the target organ and is followed by a 5-min break (= limb reperfusion). The whole schedule is performed three times for a total of three 10-min cycles (= 30 min/patient).
- Arm 2:
- Control Arm/ "sham"-RIPC: In "sham"-RIPC, a blood pressure cuff is placed around an arm immediately prior to surgery (after induction of anesthesia and before/ during incision/dissection), but NOT inflated. This is followed by a 5-min break. The whole schedule is performed three times for a total of three 10-min cycles (= 30 min/patient).
Endpoints
- Primary outcome:
- The primary endpoint is the anastomotic leakage rate within 30 days after surgery. Anastomotic leakage is defined and classified according to the recommendation of the International Study Group of Rectal Cancer (Rahbari NN et al. (2010) Definition and Grading of Anastomotic Leakage: a proposal by the International Study Group of Rectal Cancer Surgery 147 (3): 339-351). In patients with suspicious clinical symptoms (pain, fever, increased infection parameters, tachycardia / hypotension), anastomotic leakage is confirmed / excluded by endoscopic or radiographic (computed tomography with rectal contrast enema) examinations. This corresponds to the clinical standard. All asymptomatic patients will undergo an endoscopic control of anastomotic healing on postoperative day (POD) 5 (+/- 1 day) to assess the primary endpoint.
- Secondary outcome:
- Secondary endpoints are perioperative morbidity and mortality (Clavien-Dindo classification), conduit necrosis, chyle leak, recurrent nerve palsy (defined by the ECCG), need for/duration of re-interventions (endoluminal vacuum therapy, interventional drainage, re-operation), hospital/ICU stay and readmissions. Effects of RIPC on biomarkers of ischemia-reperfusion injury (serotonin, VEGF) and necrotic cell death (Hmgb1) will be measured in plasma before RIPC (t0), immediately after RIPC (t1), and at 3 hours after RIPC (t2) using ELISA.
Study Design
- Purpose:
- Prevention
- Allocation:
- Randomized controlled study
- Control:
-
- Placebo
- Phase:
- III
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- Yes
- Assignment:
- Parallel
- Sequence generation:
- No Entry
- Who is blinded:
-
- Assessor
- Data analyst
- Investigator/therapist
- Patient/subject
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Chirurgische Klinik Mannheim
Recruitment period and number of participants
- Planned study start date:
- 2019-11-25
- Actual study start date:
- 2019-12-10
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2022-06-19
- Target Sample Size:
- 56
- Final Sample Size:
- 50
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- Persons meeting the following criteria may be included in the study: • Planned elective continence-preserving rectal resection for rectal cancer • Signed informed consent • Age ≥18 years
Exclusion Criteria
Persons meeting any of the following criteria cannot be included in the study: • Patients not able to give informed consent • Patients presenting with the following contraindications to the study intervention (RIPC): arterial occlusive disease (AOD), infections or wounds on the upper extremity, poorly controlled diabetes mellitus, or deep vein thrombosis of the upper extremity
Addresses
Primary Sponsor
- Address:
- Medizinische Fakultät MannheimSeminarstr. 269117 HeidelbergGermany
- Telephone:
- +49 6221 54-2100 & -2001
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische KlinikProf. Dr. med. Julia HardtTheodor-Kutzer-Ufer 1-368167 MannheimGermany
- Telephone:
- 0621-383-2225
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.umm.de/chirurgische-klinik/
Contact for Public Queries
- Address:
- Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische KlinikProf. Dr. med. Julia HardtTheodor-Kutzer-Ufer 1-368167 MannheimGermany
- Telephone:
- 0621-383-2225
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.umm.de/chirurgische-klinik/
Principal Investigator
- Address:
- Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische KlinikProf. Dr. med. Julia HardtTheodor-Kutzer-Ufer 1-368167 MannheimGermany
- Telephone:
- 0621-383-2225
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.umm.de/chirurgische-klinik/
Sources of Monetary or Material Support
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische KlinikTheodor-Kutzer-Ufer 1-368167 MannheimGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2019-10-20
- Ethics committee number:
- 2019-730N
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2019-10-28
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry