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

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

Estonia

Study Type

Interventional

Intervention

Remote ischemic preconditioning

SHAM Remote ischemic preconditioning

About this trial

This is an interventional prevention trial for Atherosclerosis focused on measuring Remote ischemic preconditioning, Contrast-induced Nephropathy, Stable coronary artery disease, Lower extremity arterial disease, Low molecular weight metabolites, Functional properties of arteries

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Tartu University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Remote ischemic preconditioning

SHAM remote ischemic preconditioning

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Cardiac markers

N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK) MB isoenzyme, troponin T

Traditional biomarkers of renal function

Urea, creatinine

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

Estimated glomerular filtration rate

eGFR

Markers of oxidative stress and inflammation

Oxidized low density lipoprotein (oxLDL), interleukin 18 (IL-18), myeloperoxidase (MPO)

Length of hospital stay

Length of hospital stay measured in days.

Adverse events of angiographic procedures

Allergic reactions to iodinated contrast media or local anesthetics

All-cause and cardiovascular mortality

Data of 1-year all-cause and cardiovascular mortality will be collected from the Estonian Causes of Death Registry.

Adverse events associated with femoral artery puncture

Bleeding, hematoma, arterial thrombosis

Cardiac event

Myocardial infarction or cardiac arrest

Adverse events of remote ischemic preconditioning

Upper-extremity deep vein thrombosis, acute upper limb ischaemia

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.

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.

Full Information

NCT ID

NCT02700958

First Posted

February 3, 2016

Last Updated

May 16, 2018

Sponsor

Tartu University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02700958

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

February 2016 (Actual)

Primary Completion Date

March 19, 2018 (Actual)

Study Completion Date

March 19, 2019 (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tartu University Hospital

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atherosclerosis, Stable Angina, Peripheral Artery Disease, Contrast-induced Nephropathy

Keywords

Remote ischemic preconditioning, Contrast-induced Nephropathy, Stable coronary artery disease, Lower extremity arterial disease, Low molecular weight metabolites, Functional properties of arteries

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

160 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Remote ischemic preconditioning

Arm Type

Experimental

Arm Description

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.

Arm Title

SHAM remote ischemic preconditioning

Arm Type

Sham Comparator

Arm Description

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.

Intervention Type

Procedure

Intervention Name(s)

Remote ischemic preconditioning

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

SHAM Remote ischemic preconditioning

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in carotid-femoral pulse wave velocity compared with baseline and SHAM subgroup

Description

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.

Time Frame

24 hours

Title

Change in augmentation indices (augmentation index and heart rate-corrected augmentation index (AIx@75)) compared with baseline and SHAM subgroup

Description

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.

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Cardiac markers

Description

N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase (CK) MB isoenzyme, troponin T

Time Frame

24 hours

Title

Traditional biomarkers of renal function

Description

Urea, creatinine

Time Frame

24 hours

Title

Novel biomarkers of renal function

Description

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

Time Frame

24 hours

Title

Estimated glomerular filtration rate

Description

eGFR

Time Frame

24 hours

Title

Markers of oxidative stress and inflammation

Description

Oxidized low density lipoprotein (oxLDL), interleukin 18 (IL-18), myeloperoxidase (MPO)

Time Frame

24 hours

Title

Length of hospital stay

Description

Length of hospital stay measured in days.

Time Frame

30 days

Title

Adverse events of angiographic procedures

Description

Allergic reactions to iodinated contrast media or local anesthetics

Time Frame

7 days

Title

All-cause and cardiovascular mortality

Description

Data of 1-year all-cause and cardiovascular mortality will be collected from the Estonian Causes of Death Registry.

Time Frame

1 year

Title

Adverse events associated with femoral artery puncture

Description

Bleeding, hematoma, arterial thrombosis

Time Frame

24 hours

Title

Cardiac event

Description

Myocardial infarction or cardiac arrest

Time Frame

30 days

Title

Adverse events of remote ischemic preconditioning

Description

Upper-extremity deep vein thrombosis, acute upper limb ischaemia

Time Frame

10 days

Title

Low molecular weight metabolites

Description

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.

Time Frame

24 hours

Title

Arterial elasticity indices

Description

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.

Time Frame

24 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials: