HypertensionINSPiREDNCT01505010

Renal Denervation for Management of Drug-Resistant Hypertension

A study testing Renal denervation in people with Hypertension, run by KU Leuven at 2 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 20 to 69 years
Conditions the study is for: Hypertension
What is being tested?: Renal denervation
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 2 sitesBelgium
Study dates: Apr 2014to 31 Mar 2017
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 to 69 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

Belgium2 sites

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

Other trials in Belgium

About this study

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

Read the 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.

Conditions: Hypertension
Being tested: Renal denervation
Keywords: Treatment-resistant hypertension, Renal denervation, Sympathetic nervous system
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Renal denervationProcedure or surgery
Also called Renal denervation, using an intravascular catheter system
Renal denervation in the intervention group

Study groups in NCT01505010
Study group	Role	What they receive
Control group	Other	Standard antihypertensive drug treatment Receives: Procedure: Renal denervation
Intervention group	Experimental	Renal denervation plus standard antihypertensive drug treatment Receives: Procedure: Renal denervation

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Systolic Blood Pressure From Baseline to 6 Months on 24-h Ambulatory Measurement (Follow-up Minus Baseline Measurement)
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.
Measured: The primary endpoint has been assessed 6 months after randomization.
Change in Glomerular Filtration Rate
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.
Measured: This endpoint has been assessed 6 months after randomization.

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 201431 Mar 2017

First posted6 Jan 2012 (estimated)
Study startApr 2014
Primary completion31 Dec 2016
Study completion31 Mar 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by KU LeuvenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Parallel group trial
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01505010
Sponsor's protocol ID: INSPiRED, version 4.0
Acronym: INSPiRED
Status last verified: Mar 2020
First submitted: 3 Jan 2012
Last updated: 27 Mar 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: 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.

Publications

Jacobs L, Persu A, Huang QF, Lengele JP, Thijs L, Hammer F, Yang WY, Zhang ZY, Renkin J, Sinnaeve P, Wei FF, Pasquet A, Fadl Elmula FEM, Carlier M, Elvan A, Wunder C, Kjeldsen SE, Toennes SW, Janssens S, Verhamme P, Staessen JA; European Network Coordinating Research on Renal Denervation. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension. Blood Press. 2017 Dec;26(6):321-331. doi: 10.1080/08037051.2017.1320939. Epub 2017 May 10.
PubMed 28489464
Jin Y, Jacobs L, Baelen M, Thijs L, Renkin J, Hammer F, Kefer J, Petit T, Verhamme P, Janssens S, Sinnaeve P, Lengele JP, Persu A, Staessen JA; investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) investigators. Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial. Blood Press. 2014 Jun;23(3):138-46. doi: 10.3109/08037051.2014.899297. Epub 2014 Apr 17.
PubMed 24742341

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension

All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension
ClinicalTrials.gov ID: NCT01505010
Acronym / sponsor ID: INSPiRED / INSPiRED, version 4.0
Conditions: Hypertension
Keywords: Treatment-resistant hypertension, Renal denervation, Sympathetic nervous system
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: KU LeuvenUniversity, hospital or other
Study start: Apr 2014 (actual)
Primary completion: 31 Dec 2016 (actual)
Study completion: 31 Mar 2017 (actual)
First posted: 6 Jan 2012 (estimated)
Results: Posted 27 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Objectives:

Trial design:

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:

Assessment of adherence:

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:

Relevance:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Parallel group trial

Arm	Type	Receives
Control group	Other	Procedure: Renal denervationStandard antihypertensive drug treatment
Intervention group	Experimental	Procedure: Renal denervationRenal denervation plus standard antihypertensive drug treatment

Who may qualify

Ages: 20 to 69 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Renal denervationAlso: Renal denervation, using an intravascular catheter systemRenal denervation in the intervention group	Procedure or surgery	Control group, Intervention group

Primary outcome

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.
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.

1 secondary outcome

The Intensity of Medical Treatment
Time frame: This endpoint will be assessed 6 months after randomization.

Results and safety

Results posted to the registry on 27 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control Group	9	9
Intervention Group	8	6

Primary outcome: 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.. Mean (95% Confidence Interval). Unit: mmHg

Measure	Control Group n = 9	Intervention Group n = 6
Value	0.7 (-12.0 to 13.4)	-21.7 (-33.4 to -9.9)

Control Group vs Intervention Group: Mean Difference (Final Values): 22.4, p = 0.018, Mixed Models Analysis

Primary outcome: Change in Glomerular Filtration Rate

Time frame: This endpoint has been assessed 6 months after randomization.. Mean (Standard Deviation). Unit: ml/min/1.73 m2

Measure	Control Group n = 9	Intervention Group n = 6
Value	81.6 (24.1)	92.4 (15.9)

Control Group vs Intervention Group: Mean Difference (Net): 2.5, p = 0.86, t-test, 2 sided

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Group	0 of 9 (0%)	0 of 9 (0%)	0 of 9
Intervention Group	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Limitations and caveats (from the sponsor): Ethical approval was obtained to randomise 18 patients in a pilot trial, published recently (http://dx.doi.org/10.1080/08037051.2017.1320939)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28489464Jacobs L, Persu A, Huang QF, Lengele JP, Thijs L, Hammer F, Yang WY, Zhang ZY, Renkin J, Sinnaeve P, Wei FF, Pasquet A, Fadl Elmula FEM, Carlier M, Elvan A, Wunder C, Kjeldsen SE, Toennes SW, Janssens S, Verhamme P, Staessen JA; European Network Coordinating Research on Renal Denervation. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension. Blood Press. 2017 Dec;26(6):321-331. doi: 10.1080/08037051.2017.1320939. Epub 2017 May 10.
Derived from this study: PubMed 24742341Jin Y, Jacobs L, Baelen M, Thijs L, Renkin J, Hammer F, Kefer J, Petit T, Verhamme P, Janssens S, Sinnaeve P, Lengele JP, Persu A, Staessen JA; investigator-steered project on intravascular renal denervation for management of drug-resistant hypertension (INSPiRED) investigators. Rationale and design of the Investigator-Steered Project on Intravascular Renal Denervation for Management of Drug-Resistant Hypertension (INSPiRED) trial. Blood Press. 2014 Jun;23(3):138-46. doi: 10.3109/08037051.2014.899297. Epub 2014 Apr 17.
Individual participant dataSharing planned: Yes. 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.

Related trials for Hypertension

Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Enrolling by invitation
Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle
Pregnancy Related, Hypertension

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jan A. Staessen, MD, PhD principal investigator

University of Leuven

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Renal denervation in people with Hypertension, run by KU Leuven at 2 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01505010, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2020.