Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED)

March 15, 2020 updated by: Jan A. Staessen, KU Leuven

Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension

INSPiRED is a multicenter parallel-group trial comparing usual medical treatment (control group) or usual medical treatment plus renal denervation (intervention). In both groups adherence will be monitored both before randomization and during 36 months of follow-up.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objectives:

To compare the blood pressure lowering efficacy and safety of renal denervation vs. usual medical therapy. The primary endpoints for efficacy and safety are the baseline-adjusted between-group differences in 24-h systolic blood pressure and in glomerular filtration rate as estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Secondary endpoints for efficacy and safety include other indexes of blood pressure control and renal function, metabolic variables and morbidity and mortality. These endpoints will be assessed 6 months after randomization.

Trial design:

Randomized controlled trial with blinded assessment of the primary and secondary endpoints. The study consists of 6 stages. Supervised and nonsupervised follow-up refer to assessment of outcome at or outside the participating center, respectively.

  • Screening involves checking eligibility and ruling out secondary hypertension.
  • Run-in period of 3 months to optimize medical treatment and to assess adherence to treatment.
  • Stratification and randomization Eligible patients will be stratified by center and age group (adults vs. elderly, 20-49 vs. 50-69 years) and randomized centrally in a one-to-one proportion to control or intervention.
  • Renal sympathetic denervation in the intervention group, patients of the control group will be offered renal denervation after 6 months.
  • Supervised follow-up at 1, 3 and 6 months after randomization.
  • Long-term supervised or non-supervised follow-up of morbidity and mortality beyond 6 months and up to 3 years.

Sample size:

To detect a 10-mm Hg difference (SD 20 mm Hg) in systolic blood pressure between the randomized groups with a 2-sided P-value of 0.01 and 90% power in total 240 patients need to be randomized. Allowing 50% screening failures, 480 patients would have to be screened.

Assessment of adherence:

Adherence to treatment will be assessed by measurement of drugs or drug metabolites in biological fluids. Jung and coworkers developed a liquid chromatography-mass spectrometric method that allows detecting all antihypertensive drugs or their metabolites in a single urine sample. This obligatory approach will be implemented.

Assessment of quality of life Assessment of quality of life is compulsory at baseline and at each visit during the supervised follow-up, using the EuroQol 5D.

Assessment of sympathetic modulation:

heart rate variability (HRV) will be assessed at baseline and at the 6-month follow-up visit, based on 15 minutes ECG recordings. A software program, developed in LabVIEW by the group of Aubert et al. will be used.

Relevance:

INSPiRED differs from previous and ongoing studies in several aspects: (1) a stringent selection of patients; (2) drug optimization with assessment of adherence throughout the study; (3) out-of-the-office blood pressure for patient selection and follow-up; (4) state-of-the-art renal artery imaging by computerized tomographic angiography; (5) validation of urinary proteomic biomarkers to predict blood pressure responses and changes in renal function; (6) follow-up will be beyond 6 months up to 3 years; (7) use of heart rate variability and renal nerve stimulation to assess the completeness of renal denervation.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, BE-1200
        • Cliniques Universitaires Saint-Luc
      • Leuven, Belgium, BE-3000
        • Universitair Ziekenhuis Gasthuisberg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Women and men are eligible. Women of reproductive age should apply effective contraception.
  • Age ranges from 20 years (inclusive) to less than 70 years.
  • Patients should have essential hypertension.
  • Treatment-resistant hypertension in patients taking a stable drug regimen for at least 4 weeks consisting of 3 or more antihypertensive medications from different classes, including a diuretic.
  • Under maximal therapy, office blood pressure should be ≥140/90 mmHg and the 24-h ambulatory blood pressure should be 130 mm Hg systolic or 80 mm Hg diastolic or higher.
  • eGFR must be ≥ 60 mL/min/1.73 m2.
  • The patients should accept to have adherence checked before randomisation and during supervised follow-up, but both patients and doctors will remain blinded to the results;
  • Informed written consent.

Exclusion criteria:

  • Suboptimal clinical context, because of recent history or concurrent disease.
  • Isolated systolic and diastolic hypertension.
  • Body-mass index ≥ 40kg/m2.
  • The anatomy of the renal arteries is suboptimal for renal denervation.
  • Pregnancy.
  • Alcohol or substance abuse or psychiatric illnesses.
  • Participation in other study.
  • The clinical context is suboptimal for renal denervation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Control group
Standard antihypertensive drug treatment
Procedure: Renal denervation
Renal denervation in the intervention group
Other Names:
  • Renal denervation, using an intravascular catheter system
Experimental: Intervention group
Renal denervation plus standard antihypertensive drug treatment
Procedure: Renal denervation
Renal denervation in the intervention group
Other Names:
  • Renal denervation, using an intravascular catheter system

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Systolic Blood Pressure From Baseline to 6 Months on 24-h Ambulatory Measurement (Follow-up Minus Baseline Measurement)
Time Frame: The primary endpoint has been assessed 6 months after randomization.
The primary endpoint deals with efficacy of renal denervation with regard to controlling blood pressure on ambulatory measurement. It consists of the baseline-adjusted between-group difference in the changes in 24-h systolic blood pressure. Because automated blood pressure monitors will be used, the assessment of the primary endpoint is blind.
The primary endpoint has been assessed 6 months after randomization.
Change in Glomerular Filtration Rate
Time Frame: This endpoint has been assessed 6 months after randomization.
The primary endpoint for safety of renal denervation is the baseline-adjusted between group difference in the change of glomerular filtration rate estimated by using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.
This endpoint has been assessed 6 months after randomization.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Intensity of Medical Treatment
Time Frame: This endpoint will be assessed 6 months after randomization.
The number and doses of blood-pressure lowering drugs in the 2 arms of the trial.
This endpoint will be assessed 6 months after randomization.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

KU Leuven

Investigators

  • Principal Investigator: Jan A. Staessen, MD, PhD, University of Leuven

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2014

Primary Completion (Actual)

December 31, 2016

Study Completion (Actual)

March 31, 2017

Study Registration Dates

First Submitted

January 3, 2012

First Submitted That Met QC Criteria

January 4, 2012

First Posted (Estimate)

January 6, 2012

Study Record Updates

Last Update Posted (Actual)

March 27, 2020

Last Update Submitted That Met QC Criteria

March 15, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INSPiRED, version 4.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized data can be made available via a motivated data transfer request (for scientific purposes only) via the PI (Prof Jan A. Staessen) and pending ethics approval.

IPD Sharing Time Frame

Currently available until 2025

IPD Sharing Access Criteria

Ethics approval

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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