Trial document



drksid header

  DRKS00018934

Trial Description

start of 1:1-Block title

Title

Remote Ischemic Preconditioning (RIPC) versus sham-control for prevention of anastomotic leakage after resection for Esophageal cancer: a prospective, randomized controlled, triple-blind, clinical phase III monocenter trial

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

RIPE

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

http://no website available

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Anastomotic leakage (= suture leaking) is a dreaded complication after surgery on the esophagus. 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 pilot study is the first study that will investigate whether RIPC reduces the risk for anastomotic leakage after resection for esophageal cancer. The goal of this study is to gain enough data to plan a larger, subsequent multicenter study. During the 90-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.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

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 esophageal resection has a protective effect on the development of anastomotic leakage is still unclear. To test the feasibility (accrual rate) and in preparation for a large-scale multicenter RCT (randomized controlled trial), the pilot RCT described here was designed.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

No

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00018934
  •   2019/10/28
  •   [---]*
  •   yes
  •   Approved
  •   2019-722N, Medizinische Ethik-Kommission II Medizinische Fakultät Mannheim der Universität Heidelberg
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C15.9 -  Malignant neoplasm: Oesophagus, unspecified
  •   K91.83 -  [generalization K91.8: Other postprocedural disorders of digestive system, not elsewhere classified]
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   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).
  •   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).
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, assessor, data analyst
  •   Placebo
  •   Prevention
  •   Parallel
  •   III
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

The primary endpoint is anastomotic leakage within 90 days after surgery, which would also be the primary outcome measure for a subsequent confirmatory trial. Anastomotic leakage is defined according to the “International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy” published by the Esophagectomy Complications Consensus Group (ECCG). In line with the report on standardization of data collection for complications associated with esophagectomy, AL is defined as a full-thickness defect involving the esophagus, the anastomosis or the gastric conduit. In patients with clinical symptoms (pain, fever, elevated infectious parameters, tachycardia/hypotension), anastomotic leakage will be confirmed by endoscopic (esophagogastroduodenoscopy (EGD)) or radiologic (esophageal contrast study, computed tomography scan with esophageal contrast) investigations. Asymptomatic patients, will be evaluated on a routine basis by endoscopy on postoperative day (POD) 4 (+/-1). All endoscopists and radiologists will be blinded to the study intervention.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary 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.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2019/12/11
  •   56
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

Persons meeting the following criteria may be included in the study:
• Planned elective esophagus resection for esophageal cancer
• Signed informed consent
• Age ≥18 years

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

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

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Medizinische Fakultät Mannheim
    • Seminarstr. 2
    • 69117  Heidelberg
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   +49 6221 54-2100 & -2001
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Ms.  PD Dr. med.  Julia  Hardt 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Ms.  PD Dr. med.  Julia  Hardt 
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Universität Heidelberg, Medizinische Fakultät Mannheim, Chirurgische Klinik
    • Theodor-Kutzer-Ufer 1-3
    • 68167  Mannheim
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.