Protection by Remote Ischemic Preconditioning During Transcatheter Aortic Valve Implantation

University Hospital Essen

Status and phase: Unknown; Phase 2

Conditions: Aortic Valve Stenosis

Treatments: Procedure: Remote ischemic preconditioning (RIPC); Procedure: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02080299

135355-BO

Details and patient eligibility

About

Transcatheter aortic valve implantation (TAVI) has rapidly been adopted into clinical practice, but concerns have been raised regarding periprocedural complications like e.g. myocardial injury, stroke or acute kidney injury. Remote ischemic preconditioning (RIPC) with upper limb ischemia/reperfusion provides perioperative myocardial protection in patients undergoing elective coronary artery bypass surgery. The present study assesses protection of heart, brain and kidney by RIPC in patients undergoing TAVI. The study also addresses safety and clinical outcome.

Full description

• On the assumption of our recent data (Thielmann et al, Lancet 2013, 382(9892):597-604), we performed a power analysis, revealing an estimated enrollment of 189 patients per group. But since no true data exist regarding RIPC and TAVI, interim analysis will be performed after 50 patients per group.
• After induction of conscious sedation or general anaesthesia, RIPC is accomplished by 3 cycles of 5 min inflation/5 min deflation of a blood pressure cuff around the left arm to 200 mm Hg. In the placebo group, the blood pressure cuff remains uninflated for 30 min.
• Blind: study coordinators, outcome assessors, operators and treating physicians except for the attending anaesthetist.
• Drugs used for conscious sedation: midazolam, remifentanil.
• Drugs used for general anaesthesia: sufentanil, etomidate, rocuronium, isoflurane.
• TAVI is performed by standard techniques using the balloon-expandable Sapien XT (Edwards Lifesciences Inc., Irvine, California, USA) and the next-generation Sapien 3 stent-valve bioprosthesis which replaces the Sapien XT prosthesis, when CE-approved.
• Arterial blood samples are obtained prior to and after RIPC-maneuver/Placebo, after aortic valve implantation and after access site closure, for biochemical analyses focussing on ligands that have been previously implicated in conditioning protocols at various organs. A bioassay system, consisting of a Langendorff-perfused isolated heart with ischemia and reperfusion will be used. This bioassay system will be exposed to the obtained arterial plasma of the patients.
• Venous blood samples are drawn before TAVI and at 1, 6, 12, 24, 48 and 72 hours after the procedure.
• Cardiac and cerebral MRI is performed in selected patients at baseline and within the first week after TAVI.
• On-site follow-up at 3±3 months, 12±3 months and yearly thereafter.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with severe symptomatic native aortic valve stenosis scheduled for elective TAVI due to a prohibitive or high risk for surgical aortic valve replacement as judged by the institutional heart team based on risk scores and comorbidity assessment
• Written informed consent

Exclusion criteria

• Life expectancy < 1 year
• Patients who are unlikely to gain improvement in their quality of life by TAVI procedure
• Unfavorable anatomy for TAVI (e.g. inadequate annulus size)
• Left-ventricular thrombus
• Active endocarditis
• Active infection
• Acute ST-segment elevation myocardial infarction
• Hemodynamic instability
• Preoperative troponin I concentration above the upper normal limit of 0.1 ng/ml
• Stroke within the last 6 weeks
• Acute or chronic hemodialysis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups, including a placebo group

Remote ischemic preconditioning (RIPC)

Active Comparator group

Description:

RIPC-protocol before TAVI: after induction of conscious sedation/anesthesia, but prior to TAVI procedure, remote ischemic preconditioning (RIPC) protocol is performed, consisting of 3 cycles of 5 minutes left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 minutes of reperfusion, followed by a time interval between the end of the last deflation and local groin anaesthesia with subsequent skin puncture of 30 min.

Treatment:

Procedure: Remote ischemic preconditioning (RIPC)

Placebo

Placebo Comparator group

Description:

Placebo protocol before TAVI: After induction of conscious sedation/anesthesia and before TAVI, the cuff is left uninflated for 30 min, followed by a further time interval of 30 min until local groin anaesthesia with subsequent skin puncture.

Treatment:

Procedure: Placebo