Remote Ischaemic Conditioning on Blood Pressure Control in Chronic Kidney Disease Patients (ERIC-BP-CKD)

The Effect of Remote Ischaemic Conditioning on Blood Pressure Control in Patients With Chronic Kidney Disease - the ERIC-BP-CKD Trial

Chronic kidney disease (CKD) is one of the leading causes of death and disability in Singapore and worldwide. Hypertension is commonly inadequately controlled in patients with CKD and this is associated with CKD progression and cardiovascular complications. Daily episodes of Remote ischaemic conditioning (termed chronic RIC or CRIC) using transient limb ischaemia/reperfusion applied for 1 to 12 months have been shown to lower systemic blood pressure (SBP), prevent stroke and reduce post-myocardial infarction left ventricular (LV) remodelling in experimental and clinical studies. In the ERIC-BP-CKD feasibility and efficacy study, we hypothesise that CRIC administered for 28 days will lower systemic blood pressure and improve blood pressure control in patients with CKD and hypertension.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Hypertension; Chronic Kidney Diseases
• Intervention / Treatment: Device: Active autoRIC® (CRIC Treatment); Device: Sham Control autoRIC® (Sham Control)

Detailed Description

Chronic kidney disease (CKD) is one of the leading causes of death and disability in Singapore and worldwide. CKD patients often suffer with inadequately controlled hypertension, the presence of which is associated with cardiovascular complications such as left ventricular (LV) hypertrophy, cardiac failure, and stroke. As such, novel treatments are required to improve blood pressure control in order to improve health outcomes in CKD patients.

Remote ischaemic conditioning (RIC) using transient limb ischaemia/reperfusion has been shown to protect the kidney and microvasculature in experimental and clinical studies, and daily episodes of RIC (termed chronic RIC or CRIC) applied for 1 to 12 months have been shown to lower systemic blood pressure (SBP), prevent stroke and reduce post-myocardial infarction left ventricular (LV) remodelling in experimental and clinical studies. Whether CRIC can reduce SBP in hypertensive patients with CKD is not known. In the ERIC-BP-CKD feasibility and efficacy study, we hypothesise that CRIC administered for 28 days will lower systemic blood pressure and improve blood pressure control in patients with CKD and hypertension.

In this study, subjects will be randomised in a 1:1 ratio to receive therapy from either the active autoRIC® Device or identical sham autoRIC® Device.

• Study Type: Interventional
• Enrollment (Anticipated): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Jason Choo, MBBS; Phone Number: 65 63214436
    • Principal Investigator: Jason Choo, MBBS
    • Principal Investigator: Derek Hausenloy, MBChB, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent
2. Aged 21 years and older
3. CKD (all stages 1-4)
4. On treatment for hypertension and automated office BP (AOBP) ≥ 140mmHg (this will be determined by an automated oscillometric BP device)

Exclusion Criteria:

1. Patients with polycystic kidney disease
2. Atrial fibrillation
3. Patients on long-acting sulphonylureas (eg glibenclamide) or nicorandil (as these medications may interfere with the protective effect of CRIC).
4. Patients recruited into another study which may impact on this study.
5. Symptomatic peripheral arterial disease affecting the upper limbs (given nature of upper-limb CRIC protocol).
6. Renal transplant / Dialysis patients
7. Pregnant patients
8. Patients on any anti-coagulant medications (e.g. Warfarin)
9. For echo sub-study only: Prior myocardial infarction, BMI > 30kg/m2, known severe acrdiac valve disease, known severely impaired LVEF <35%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRIC Treatment; An autoRIC® Device will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.	Device: Active autoRIC® (CRIC Treatment); The active autoRIC® Device is programmed to go through a preset protocol of inflation and deflation cycles every session. The sessions will be repeated daily for 28 days.
Sham Comparator: Sham Control; An autoRIC® Device visually identical to that used in the CRIC protocol will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.	Device: Sham Control autoRIC® (Sham Control); The Sham Control autoRIC® Device is visually identical to the active autoRIC® Device but the simulated protocol applied comprises of vibrations of the device but no inflation of the cuff every session. The sham device provides the same sound and vibration as that of the pump inflating and the same LED indicators on the Active Unit. The sessions will be repeated daily for 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic blood pressure	Difference in change in systolic blood pressure (measured by automated office blood pressure recording) from baseline to after 28 days between CRIC versus sham control therapy.	Baseline and 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of antihypertensive medications	Reduction in number of medications required for treating hypertension	Baseline and 28 days
Central aortic systolic pressure	Central aortic systolic pressure (measured by assessing the arterial waveform after 28 days of CRIC or sham control therapy).	Baseline and 28 days
Arterial pulse waveform	The arterial pulse waveform (measured after 28 days of CRIC or sham control therapy).	Baseline and 28 days
LV systolic and diastolic function	Change in LV systolic and diastolic function assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).	Baseline and 28 days
LV wall thickness	Change in LV wall thickness assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).	Baseline and 28 days
Spot Urine Protein-Creatinine Ratio	Change in Proteinuria assessed by Spot Urine Protein-Creatinine Ratio from baseline after 28 days of CRIC or sham control therapy.	Baseline and 28 days
Serum creatinine and eGFR	Change in Renal function (assessed by serum creatinine and eGFR from baseline to after 28 days of CRIC or sham control therapy).	Baseline and 28 days
Blood biomarkers for CKD and inflammation	CRP, IL-6, PAI-1, sCD40 ligand, and TNF-alpha will be measured for CKD and inflammation following 28 days of CRIC or sham control therapy.	Baseline and 28 days

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Duke-NUS Graduate Medical School
• Investigators: Principal Investigator: Jason Choo, MBBS, Singapore General Hospital

Publications and helpful links

General Publications

• Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.
• Luca MC, Liuni A, McLaughlin K, Gori T, Parker JD. Daily ischemic preconditioning provides sustained protection from ischemia-reperfusion induced endothelial dysfunction: a human study. J Am Heart Assoc. 2013 Feb 22;2(1):e000075. doi: 10.1161/JAHA.112.000075.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: July 25, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Hypertension; Cardiovascular Disease; Chronic Kidney Disease; Proteinuria; Remote Ischemic Conditioning; Left Ventricular Hypertrophy; Central Aortic Systolic Pressure
• Additional Relevant MeSH Terms: Vascular Diseases; Urologic Diseases; Renal Insufficiency; Hypertension; Cardiovascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: SHF/CTG059/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No