Remote Ischemic Preconditioning as a Method Against Subclinical Renal Injury and Contrast-induced Nephropathy

Study of Remote Ischemic Preconditioning as a Preventative Method Against Subclinical Renal Injury and Contrast-induced Nephropathy

Contrast-induced nephropathy (CIN) has remained significant and severe complication of angiographic procedures despite the increasing use of preventative methods. It has been associated with prolonged hospital stay, high morality and the need for dialysis. Since classically used creatinine for diagnosing of CIN does not reflect the degree of tubular injury before 24-48 hours after exposure to contrast media alternative earlier biomarkers and preventative methods are needed. Remote ischemic preconditioning is a non-invasive and safe method which in some studies has been reported to protect against contrast-induced nephropathy. The purpose of this study is to evaluate the effect of remote ischemic preconditioning (RIPC) (1) as an additional method to standard treatment to prevent subclinical and clinical contrast-induced acute kidney injury and (2) to assess its effect on functional properties of arterial wall, organ damage biomarkers and low molecular weight metabolites.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Stable Angina; Peripheral Artery Disease; Contrast-induced Nephropathy
• Intervention / Treatment: Procedure: Remote ischemic preconditioning; Procedure: SHAM Remote ischemic preconditioning

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Estonia
  • Tartu County
    • Tartu, Tartu County, Estonia, 50406
      • Tartu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age greater than 18 years, no upper age limit
• Patients with stable coronary artery disease (II - III class according to the Canadian Cardiovascular Society) hospitalized for coronarography or with lower extremity arterial disease hospitalized for angiography
• Written informed consent

Exclusion Criteria:

• Pregnancy
• Age less than 18 years
• eGFR < 30 ml/min/1,73 m2
• Simultaneous participation in an other clinical trial
• Coexisting pathology of the upper-limbs limiting the use of the cuff (bilateral amputee, recent trauma, chronic ulcers, significant upper limb peripheral atherosclerosis (radial pulse not palpable on either side))
• Malignant tumor (in remission less than 5 years or ongoing treatment)
• Documented allergic reaction to iodinated contrast agent
• Acute infection (body temperature 38 degrees Celsius or higher, c reactive protein 50mg/L or higher)
• Cardiac rhythm abnormalities (atrial fibrillation, frequent supraventricular premature complexes)
• Documented myocardial infarction within 30 days
• Inability to understand the instructions of the study
• Vascular surgery in axillary region
• Unable to lie supine for 40 minutes
• Home oxygen treatment
• Documented upper limb deep vein thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remote ischemic preconditioning; Remote Ischemic Preconditioning (RIPC) is performed by inflating blood pressure cuff for 5-minutes at 200 mmHg, or if patients systolic blood pressure is higher than 200 mmHg 20 mmHg above systolic pressure, alternated with 5-minute deflation for 4 times.	Procedure: Remote ischemic preconditioning; Remote ischemic preconditioning is performed with standard blood pressure cuff on upper-arm. RIPC will be started just before the coronarography or angiography. Time between the last inflation cycle and the beginning of the procedure will be less than 60 minutes.
Sham Comparator: SHAM remote ischemic preconditioning; SHAM Remote Ischemic Preconditioning (RIPC-SHAM) is accomplished by alternating 4 cycles of 5-minute inflation with 5-minute deflation. Blood pressure cuff will be inflated to 10-20 mmHg. RIPC-SHAM is performed with standard blood pressure cuff on upper-arm.	Procedure: SHAM Remote ischemic preconditioning; SHAM Remote ischemic preconditioning is performed with standard blood pressure cuff on upper-arm. RIPC-SHAM will be started just before the coronarography or angiography. Time between the last inflation cycle and the beginning of the procedure will be less than 60 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in carotid-femoral pulse wave velocity compared with baseline and SHAM subgroup	Carotid-femoral pulse wave velocity baseline measurement is performed. Second measuring is performed 24 hours after angiographic procedure. Change from baseline will be compared between RIPC and SHAM subgroups. Measuring is performed with SphygmoCor XCEL PWA and PWV Device.	24 hours
Change in augmentation indices (augmentation index and heart rate-corrected augmentation index (AIx@75)) compared with baseline and SHAM subgroup	Augmentation indices baseline measurement is performed. Second measuring is performed 24 hours after angiographic procedure. Change from baseline will be compared between RIPC and SHAM subgroups. Measuring is performed with SphygmoCor XCEL PWA and PWV Device.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac markers	N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK) MB isoenzyme, troponin T	24 hours
Traditional biomarkers of renal function	Urea, creatinine	24 hours
Novel biomarkers of renal function	Neutrophil gelatinase-associated lipocalin (NGAL), renal liver-type fatty acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), isoprostane, cystatin C, beta-2 microglobulin	24 hours
Estimated glomerular filtration rate	eGFR	24 hours
Markers of oxidative stress and inflammation	Oxidized low density lipoprotein (oxLDL), interleukin 18 (IL-18), myeloperoxidase (MPO)	24 hours
Length of hospital stay	Length of hospital stay measured in days.	30 days
Adverse events of angiographic procedures	Allergic reactions to iodinated contrast media or local anesthetics	7 days
All-cause and cardiovascular mortality	Data of 1-year all-cause and cardiovascular mortality will be collected from the Estonian Causes of Death Registry.	1 year
Adverse events associated with femoral artery puncture	Bleeding, hematoma, arterial thrombosis	24 hours
Cardiac event	Myocardial infarction or cardiac arrest	30 days
Adverse events of remote ischemic preconditioning	Upper-extremity deep vein thrombosis, acute upper limb ischaemia	10 days
Low molecular weight metabolites	Amino acids (alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamine, glutamate, glycine, histidine, hydroxyproline, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine), acylcarnitines (free carnitine, acylcarnitine, propionylcarnitine, butyrylcarnitine, pentanoylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine, tetradecanoylcarnitine, octadecanoylcarnitine), hydroxy acids and other metabolic parameters (aconitate, α-ketoglutarate, β-hydroxybutyrate, citrate, citrulline, 7-ketocholesterol, lactate, malonate, oxaloacetate, pyruvate, succinate) will be measured.	24 hours
Arterial elasticity indices	Arterial elasticity indices baseline measurement is performed. Second measuring is performed 24 hours after angiographic procedure. Change from baseline will be compared between RIPC and SHAM subgroups. Measuring is performed with HD/PulseWave™ CR-2000.	24 hours

Collaborators and Investigators

• Sponsor: Tartu University Hospital
• Investigators: Study Chair: Jaan Eha, MD, PhD, Tartu University Hospital; Principal Investigator: Jaak Kals, MD, PhD, Tartu University Hospital; Study Chair: Mihkel Zilmer, MD, PhD, University of Tartu; Study Director: Karl Kuusik, MD, University of Tartu; Study Chair: Teele Kepler, MD, University of Tartu

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): March 19, 2018
• Study Completion: March 19, 2019

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: March 4, 2016
• First Posted (Estimate): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Stable coronary artery disease; Remote ischemic preconditioning; Contrast-induced Nephropathy; Lower extremity arterial disease; Low molecular weight metabolites; Functional properties of arteries
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Pain; Neurologic Manifestations; Chest Pain; Peripheral Vascular Diseases; Angina Pectoris; Kidney Diseases; Peripheral Arterial Disease; Atherosclerosis; Angina, Stable
• Other Study ID Numbers: 16003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED