Overview

This trial is active, not recruiting.

Condition aortic valve stenosis
Treatments remote ischemic preconditioning (ripc), placebo
Phase phase 2
Sponsor University Hospital, Essen
Collaborator Koblenz University of Applied Science
Start date September 2013
End date August 2017
Trial size 100 participants
Trial identifier NCT02080299, 135355-BO

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (investigator)
Primary purpose treatment
Arm
(Active Comparator)
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.
remote ischemic preconditioning (ripc)
3 circles of 5 min left upper arm ischemia by inflation of a blood pressure cuff to 200 mmHg and 5 min reperfusion, preceding TAVI procedure.
(Placebo Comparator)
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.
placebo
Prior to TAVI-procedure, the blood pressure cuff remains uninflated for 30 min.

Primary Outcomes

Measure
Extent of periinterventional myocardial injury as reflected by the geometric mean of the area under the curve (AUC) for troponin I serum concentrations
time frame: 72 hours postinterventionally after TAVI

Secondary Outcomes

Measure
Periprocedural myocardial infarction according to current Valve Academic Research Consortium (VARC-2) criteria
time frame: 72 hours postinterventionally after TAVI
Incidence of new wall abnormalities and deterioration of overall left ventricular function as assessed by postinterventional transthoracic echocardiography
time frame: Within the first week after TAVI
Incidence of new-onset cardiac arrhythmias including the necessity of defibrillation or transient/permanent pacemaker implantation as assessed by continuous ECG-monitoring
time frame: Within the first week after TAVI
Prevalence and volume of delayed gadolinium enhancement
time frame: Within the first week after TAVI
Maximum elevation of serum creatinine concentration
time frame: Until 72 hours after TAVI
Maximum decrease of estimated glomerular filtration rate
time frame: Until 72 hours after TAVI
Incidence of VARC-2 defined acute kidney injury
time frame: Until 72 hours after TAVI and until discharge
Total and median per patient number as well as total and median per patient volume of new foci of restricted diffusion
time frame: Within the first week after TAVI
Cardioprotective factor release into circulating blood
time frame: Day of intervention
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) at 30 days
time frame: Within the first 30 days after TAVI
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) at 1 year
time frame: Within the first year after TAVI
All cause mortality and major adverse cardiac and cerebrovascular events (MACCE) after 3 months
time frame: Until 3 months after TAVI
VARC-2 defined combined early TAVI safety endpoint at 30 days
time frame: Until 30 days after TAVI

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Protection of Heart, Brain and Kidney by Remote Ischemic Preconditioning in Patients Undergoing Transcatheter Aortic Valve Implantation - a Randomized, Single-blind Study
Principal investigator Philipp Kahlert, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University Hospital, Essen.