Radiofrequency Ablation for ADPKD Blood Pressure and Disease Progression Control

Phase 2

• Conditions: Hypertension; Autosomal Dominant Polycystic Kidney Disease
• Interventions: Drug: antihypertensive drugs; Procedure: renal sympathetic denervation

• Registration Number: NCT01932450
• Lead Sponsor: Mei changlin

Brief Summary

A randomized, open-label single-center study investigates the efficacy and safety of bilateral renal artery sympathetic denervation by catheter-based radiofrequency ablation on blood pressure and disease progression control in autosomal dominant polycystic kidney disease(ADPKD). The total number of study subjects will be 100. All of them have diagnosed with ADPKD and hypertension. Patients will be randomized 1:1 (50 with radiofrequency ablation(RFA), 50 only with drugs). Change in average office-based measurements of systolic blood pressure(SBP), average 24-hour systolic blood pressure by ambulatory blood pressure monitoring (ABPM) , incidence of office systolic blood pressure reductions of ≥10, ≥15 and ≥20 mm Hg , office diastolic blood pressure (DBP), number and dosage of blood pressure tablets, total kidney volume (TKV), total cyst volume (TCV), pain related to cystic kidneys and renal function, will be assessed at 12 months of follow-up. The safety variables will be assessed at every visit of follow-up.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-08-18
• Study First Submitted QC: 2013-08-27
• Study First Posted: 2013-08-30
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-23
• Last Update Posted: 2014-09-25
• Primary Completion: 2014-12
• Study Completion: 2015-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients with ADPKD.
• Having hypertension, defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, and currently using 2 antihypertensive drugs and receiving a stable antihypertensive treatment regimen without change in dose or medication in the previous 30 days.
• Male and female patients 20 years to 60 years of age.
• Glomerular Filtration Rate (GFR) ≥30 ml/min/1.73 m2, estimated from serum creatinine using the Chronic Kidney Disease Epidemiology collaboration(CKD-EPI) equation.
• Have followed-up kidney and cyst volume at least 6 months in Shanghai Changzheng Hospital.
• Signed Informed Consent after being informed.

Exclusion Criteria

• Documented renal vascular disease.
• Congenital absence of a kidney.
• Systemic illness with renal involvement.
• Spot urine albumin-to-creatinine ratio of >0.5 g/g and/or findings suggestive of kidney disease other than ADPKD.
• Exclusions specific to MRI acquisition and measurement: cardiac pacemaker, presence of MRI incompatible metallic clips or other material, excessive body weight, untreatable claustrophobia.
• Contraindications to the catheter-based renal denervation procedure by RFA, including allergy to radioiodinated contrast agents. Anatomical abnormalities of the renal arteries which preclude RFA: presence in either kidneys of multiple main renal arteries, main renal artery stenosis >50%, or main renal arteries of <4 mm in diameter or <20 mm in length.
• Contraindications on ethical grounds.
• Women who are pregnant or breast feeding.
• Intention to become pregnant during the course of the study.
• Lack of safe contraception: Female subjects of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Female subjects who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential).
• Other clinically significant concomitant disease states (hepatic dysfunction, cardiovascular disease, metastatic cancer).
• Known or suspected non-compliance, drug or alcohol abuse.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia or confusional state of the subject.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Previous enrolment into the current study.
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
antihypertensive drugs	antihypertensive drugs	Blood pressure control in ADPKD patients with hypertension only using antihypertensive drugs which at least include an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB)
renal sympathetic denervation	antihypertensive drugs	One-time standard bilateral renal sympathetic denervation by catheter-based radiofrequency ablation and using antihypertensive drugs which at least include an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB).
renal sympathetic denervation	renal sympathetic denervation	One-time standard bilateral renal sympathetic denervation by catheter-based radiofrequency ablation and using antihypertensive drugs which at least include an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB).

Primary Outcome Measures

Name	Time	Method
office-based measurements of systolic blood pressure	baseline and 12 months (day 360±14)	Between-group change in average office-based measurements of systolic blood pressure from baseline to 12 months after randomization and One-time standard bilateral renal sympathetic denervation by catheter-based radiofrequency ablation.

Secondary Outcome Measures

Name	Time	Method
total kidney volume (TKV)	baseline and 12 months (day 360±14)	Change in total kidney volume (TKV) from baseline to 12 months
Renal artery lesion	up to 1 year (after radiofrequency ablation)	Renal artery lesion (perforation or dissection).
New renal artery stenosis	up to 1 year (after radiofrequency ablation)	New renal artery stenosis \>70%, determined by MRI within 12 months of randomization.
Embolic events	up to 1 year (after radiofrequency ablation)	Embolic events.
24-hour systolic blood pressure by ambulatory blood pressure monitoring (ABPM)	baseline and 12 months (day 360±14)	Change in average 24-hour systolic blood pressure by ambulatory blood pressure monitoring (ABPM) from baseline to 12 month.
office diastolic blood pressure	baseline and 12 months (day 360±14)	Change in office diastolic blood pressure from baseline to 12 months.
Incidence of office systolic blood pressure reduction	baseline and 12 months (day 360±14)	Incidence of office systolic blood pressure reductions of ≥10, ≥15 and ≥20 mm Hg from baseline to 12 month.
number and dosage of blood pressure tablets	baseline and 12 months (day 360±14)	Change in number and dosage of blood pressure tablets from baseline to 12 months.
estimated Glomerular Filtration Rate(eGFR)	baseline and 12 months (day 360±14)	Change in estimated Glomerular Filtration Rate(eGFR) from baseline to 12 months.
albuminuria	baseline and 12 months (day 360±14)	Change in albuminuria from baseline to 12 months.
procedure-related complications at femoral puncture site	up to 1 year (after radiofrequency ablation)	Occurrence of procedure-related complications at femoral puncture site (hematoma, arteriovenous fistula, pseudoaneurysma).
hypotension	up to 1 year (after radiofrequency ablation)	Episodes of hypotension.
acute kidney injury	up to 1 year (after radiofrequency ablation)	Acute deterioration of renal function
total cyst volume (TCV)	baseline and 12 months (day 360±14)	Change in total cyst volume (TCV) from baseline to 12 months
hypertension.	up to 1 year (after radiofrequency ablation)	Episodes of hypertension.
pain	baseline and 12 months (day 360±14)	Change in pain related to cystic kidneys from baseline to 12 months.

Trial Locations

Locations (1)

Department of Nephrology, Shanghai Changzheng Hospital; 🇨🇳 Shanghai, Shanghai, China