Remote Ischaemic Conditioning on Blood Pressure Control in Chronic Kidney Disease Patients

Not Applicable

• Conditions: Hypertension; Chronic Kidney Diseases; Cardiovascular Diseases
• Interventions: Device: Active autoRIC® (CRIC Treatment); Device: Sham Control autoRIC® (Sham Control)

• Registration Number: NCT03236350
• Lead Sponsor: Singapore General Hospital

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-07-25
• Study First Submitted QC: 2017-07-31
• Study First Posted: 2017-08-01
• Study Start: 2017-11-28
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-19
• Last Update Posted: 2019-09-23
• Primary Completion: 2020-03-31
• Study Completion: 2020-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 85

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CRIC Treatment	Active autoRIC® (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.
Sham Control	Sham Control autoRIC® (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.

Primary Outcome Measures

Name	Time	Method
Systolic blood pressure	Baseline and 28 days	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.

Secondary Outcome Measures

Name	Time	Method
LV wall thickness	Baseline and 28 days	Change in LV wall thickness assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).
Number of antihypertensive medications	Baseline and 28 days	Reduction in number of medications required for treating hypertension
Central aortic systolic pressure	Baseline and 28 days	Central aortic systolic pressure (measured by assessing the arterial waveform after 28 days of CRIC or sham control therapy).
Arterial pulse waveform	Baseline and 28 days	The arterial pulse waveform (measured after 28 days of CRIC or sham control therapy).
Serum creatinine and eGFR	Baseline and 28 days	Change in Renal function (assessed by serum creatinine and eGFR from baseline to after 28 days of CRIC or sham control therapy).
Blood biomarkers for CKD and inflammation	Baseline and 28 days	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.
LV systolic and diastolic function	Baseline and 28 days	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).
Spot Urine Protein-Creatinine Ratio	Baseline and 28 days	Change in Proteinuria assessed by Spot Urine Protein-Creatinine Ratio from baseline after 28 days of CRIC or sham control therapy.

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore