The TARGET BP OFF-MED Trial

NCT03503773 — Phase 2, Completed, 350 participants, Ablative Solutions, Inc.

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A Phase 2, Multicenter, Blinded, Sham Procedure-Controlled Trial of Renal Denervation by the Peregrine System Kit, in Subjects With Hypertension, in the Absence of Antihypertensive Medications

Registry	NCT03503773
Status	Completed
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	350 (Actual)
Sponsor	Ablative Solutions, Inc. (Industry)
Conditions	Hypertension, Hypertension,Essential
Interventions	Alcohol, Sham control (Drug, other)
Dates	start 2018-09-24, primary completion 2022-01-31, completion 2024-01-10, first posted 2018-04-20, last updated 2025-05-14
Locations	4 sites in Belgium, France, Germany, United Kingdom

-Summary

To obtain an assessment of the efficacy and safety of renal denervation by alcohol-mediated neurolysis using the Peregrine Kit in hypertensive subjects in the absence of antihypertensive medications.

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+Arms and interventions

Arm	Type	Interventions	Description
Treatment Arm:	Experimental	Drug: Alcohol	Renal denervation (using the Peregrine Kit) performed with alcohol infused through the Peregrine Catheter
Sham Control Arm	Sham comparator	Other: Sham control	Only renal angiography performed

Alcohol (Drug): Alcohol is directly infused/delivered to the adventitial and periadventitial space of the renal arteries
Sham control (Other): endovascular, renal angiography

+Outcome measures

Primary outcomes

Changes in Systolic Ambulatory Blood Pressure [Baseline to 8 weeks post-treatment]: Change from baseline in mean 24-hour ambulatory systolic blood pressure

Secondary outcomes

Change in Mean 24-Hour Ambulatory Systolic Blood Pressure at 6 Months [6 months]: Change from baseline in mean 24-hour ambulatory systolic blood pressure from baseline to 6 months
Change in Mean 24-Hour Ambulatory Systolic Blood Pressure at 12 Months [12 months]: Change from baseline in mean 24-hour systolic blood pressure at 12 months post-procedure
Change in Office SBP at 8 Weeks [8 weeks]: Change from Baseline in mean office SBP to Week 8
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 8 Weeks [8 weeks]: Change from baseline in mean 24-hour ambulatory diastolic blood pressure and 8 weeks post-procedure
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 6 Months [6 months]: Change from baseline in mean 24-hour ambulatory diastolic blood pressure at 6 months post-procedure
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 12 Months [12 months]: Change from baseline in mean 24-hour diastolic blood pressure 12 months post-procedure
Number of Participants With Major Adverse Events (MAEs) [30 days post procedure]: Number of participants with major adverse events (MAEs) 30 days post-procedure
Use of Antihypertensive Medication(s) [8 weeks]: Use of antihypertensive medication at 8 weeks
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 8 Weeks [8 weeks]: Change from Baseline in Mean Daytime Ambulatory Systolic Blood Pressure to 8 Weeks
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 6 Months [6 months]: Change from Baseline in Mean Daytime Ambulatory Systolic Blood Pressure to 6 Months
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 12 Months [12 months]: Change from Baseline in Mean Daytime Ambulatory Systolic Blood Pressure to 12 Months
Mean Daytime Ambulatory Diastolic Blood Pressure [8 weeks]: Change from Baseline in Mean Daytime Ambulatory Diastolic Blood Pressure to 8 Weeks
Change in Mean Daytime Ambulatory Diastolic Blood Pressure at 6 Months [6 months]: Change from Baseline in Mean Daytime Ambulatory Diastolic Blood Pressure to 6 months
Change in Mean Daytime Ambulatory Diastolic Blood Pressure at 12 Months [12 months]: Change from Baseline in Mean Daytime Ambulatory Diastolic Blood Pressure to 12 Months
Change in Mean Nighttime Ambulatory Systolic Blood Pressure at 8 Weeks [8 weeks]: Change from Baseline in Mean Nighttime Ambulatory Systolic Blood Pressure to 8 Weeks
Change in Mean Nighttime Ambulatory Systolic Blood Pressure at 6 Months [6 months]: Change from Baseline in Mean Nighttime Ambulatory Systolic Blood Pressure to 6 Months
Change in Mean Nighttime Ambulatory Systolic Blood Pressure to 12 Months [12 months]: Change from Baseline in Mean Nighttime Ambulatory Systolic Blood Pressure to 12 Months
Change in Mean Nighttime Ambulatory Diastolic Blood Pressure at 8 Weeks [8 weeks]: Change from Baseline in Mean Nighttime Ambulatory Diastolic Blood Pressure to 8 weeks
Change in Mean Nighttime Ambulatory Diastolic Blood Pressure at 6 Months [6 months]: Change from Baseline in Mean Nighttime Ambulatory Diastolic Blood Pressure to 6 Months
Change in Mean Nighttime Ambulatory Diastolic Blood Pressure at 12 Months [12 months]: Change from Baseline in Mean Nighttime Ambulatory Diastolic Blood Pressure to 12 Months
Change in Mean Office SBP at 6 Months [6 months]: Change from Baseline in mean office SBP to 6 Months
Change in Mean Office SBP to 12 Months [12 months]: Change from Baseline in mean office SBP to 12 Months
Change in Mean Office DBP to 8 Weeks [8 weeks]: Change from Baseline in mean office DBP to 8 Weeks
Change in Mean Office DBP to 6 Months [6 months]: Change from Baseline in mean office DBP to 6 Months
Change in Mean Office DBP at 12 Months [12 months]: Change from Baseline in mean office DBP to 12 Months

+Eligibility

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Has 3 office blood pressure measurements with a mean office systolic blood pressure (SBP) of ≥140 mmHg and ≤180 mmHg, AND a mean office diastolic blood pressure (DBP) of ≥90 mmHg.
2. Subject is willing to discontinue any current antihypertensive medications during the run-in period and the post-treatment period.
3. Has a mean 24-hour ambulatory SBP of ≥135 mmHg and ≤170 mmHg with ≥70% valid readings

Exclusion Criteria:

1. Subject has renal artery anatomy abnormalities.
2. Subject has an estimated glomerular filtration rate (eGFR) of ≤45 mL/min/1.73 m2, based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; or is on chronic renal replacement therapy.
3. Subject has documented sleep apnea.
4. Subject has any of the following conditions: severe cardiac valve stenosis, heart failure (New York Heart Association \[NYHA\] Class III or IV), chronic atrial fibrillation, and known primary pulmonary hypertension (>60 mmHg pulmonary artery or right ventricular systolic pressure).
5. Subject is pregnant or lactating at the time of enrollment or planning to become pregnant during the trial time period (female subjects only).
6. Subject is being treated chronically (e.g. daily use) with NSAIDs, immunosuppressive medications, or immunosuppressive doses of steroids. Aspirin therapy and nasal pulmonary inhalants are allowed.
7. Subject has a history of myocardial infarction, unstable angina pectoris, or stroke/TIA within 6 months prior to the planned procedure.

+Posted results

Participant flow

Milestone	Sham Control Arm	Treatment Arm:
Started	56	50
Completed	44	43
Not completed	12	7

Outcome results

Changes in Systolic Ambulatory Blood Pressure (Primary), Mean, mmHg: Sham Control Arm -1.4 +/- 8.6; Treatment Arm: -2.9 +/- 7.4 (p 0.2682)
Change in Mean 24-Hour Ambulatory Systolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 135.1 +/- 11.7; Treatment Arm: 134.1 +/- 11.6 (p 0.6964)
Change in Mean 24-Hour Ambulatory Systolic Blood Pressure at 12 Months (Secondary), Mean, mmHg: Sham Control Arm 133.7 +/- 11.3; Treatment Arm: 137.6 +/- 11.4 (p 0.0775)
Change in Office SBP at 8 Weeks (Secondary), Mean, mmHg: Sham Control Arm 160.6 +/- 16.3; Treatment Arm: 155.4 +/- 14.3
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 8 Weeks (Secondary), Mean, mmHg: Sham Control Arm 91.0 +/- 6.8; Treatment Arm: 92.2 +/- 7.6 (p 0.4734)
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 83.4 +/- 9.0; Treatment Arm: 83.0 +/- 8.4
Change in Mean 24-Hour Ambulatory Diastolic Blood Pressure at 12 Months (Secondary), Mean, mmHg: Sham Control Arm 81.0 +/- 7.9; Treatment Arm: 85.6 +/- 8.7 (p 0.0341)
Number of Participants With Major Adverse Events (MAEs) (Secondary), Count of participants, Participants: Sham Control Arm 1; Treatment Arm: 1
Use of Antihypertensive Medication(s) (Secondary), Mean, medications: Sham Control Arm 0.089 +/- 0.288; Treatment Arm: 0.060 +/- 0.240 (p 0.573)
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 8 Weeks (Secondary), Mean, mmHg: Sham Control Arm 153.2 +/- 12.0; Treatment Arm: 150.6 +/- 10.5
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 140.6 +/- 12.3; Treatment Arm: 139.7 +/- 12.8
Change in Mean Daytime Ambulatory Systolic Blood Pressure at 12 Months (Secondary), Mean, mmHg: Sham Control Arm 140.1 +/- 12.1; Treatment Arm: 143.5 +/- 12.6
Mean Daytime Ambulatory Diastolic Blood Pressure (Secondary), Mean, mmHg: Sham Control Arm 94.7 +/- 9.7; Treatment Arm: 95.2 +/- 7.5
Change in Mean Daytime Ambulatory Diastolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 87.6 +/- 9.0; Treatment Arm: 87.8 +/- 9.2
Change in Mean Daytime Ambulatory Diastolic Blood Pressure at 12 Months (Secondary), Mean, mmHg: Sham Control Arm 86.0 +/- 8.7; Treatment Arm: 90.4 +/- 9.6
Change in Mean Nighttime Ambulatory Systolic Blood Pressure at 8 Weeks (Secondary), Mean, mmHg: Sham Control Arm 136.9 +/- 14.6; Treatment Arm: 134.4 +/- 11.6
Change in Mean Nighttime Ambulatory Systolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 125.6 +/- 13.9; Treatment Arm: 125.4 +/- 12.1
Change in Mean Nighttime Ambulatory Systolic Blood Pressure to 12 Months (Secondary), Mean, mmHg: Sham Control Arm 123.1 +/- 12.3; Treatment Arm: 127.8 +/- 10.7
Change in Mean Nighttime Ambulatory Diastolic Blood Pressure at 8 Weeks (Secondary), Mean, mmHg: Sham Control Arm 82.5 +/- 12.4; Treatment Arm: 81.5 +/- 8.4
Change in Mean Nighttime Ambulatory Diastolic Blood Pressure at 6 Months (Secondary), Mean, mmHg: Sham Control Arm 75.8 +/- 10.8; Treatment Arm: 75.5 +/- 9.2
6 more outcome measures not shown.

Adverse events

Time frame: 12 months

Arm	Deaths	Serious adverse events	Other adverse events
Sham Control Arm	0/56 (0.0%)	9/56 (16.1%)	42/56 (75.0%)
Treatment Arm:	0/50 (0.0%)	7/50 (14.0%)	41/50 (82.0%)

Serious adverse events by term

Term	Organ system	Sham Control Arm	Treatment Arm:
Atrial fibrillation	Cardiac disorders	0/56	2/50
Abdominal abscess	Infections and infestations	0/56	1/50
Appendicitis perforated	Infections and infestations	0/56	1/50
Post procedural haematoma	Injury, poisoning and procedural complications	0/56	1/50
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	1/56	0/50
Haemoglobin decreased	Investigations	1/56	0/50
Hyponatraemia	Metabolism and nutrition disorders	1/56	0/50
Lumbar vertebral fracture	Musculoskeletal and connective tissue disorders	1/56	0/50
Sciatica	Nervous system disorders	1/56	0/50
Urethral stenosis	Renal and urinary disorders	0/56	1/50
Lung neoplasm malignant	Respiratory, thoracic and mediastinal disorders	1/56	0/50
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	1/56	0/50
Mitral valve repair	Surgical and medical procedures	1/56	0/50
Aneurysm	Vascular disorders	0/56	1/50
Haematoma	Vascular disorders	0/56	1/50
Hypertensive crisis	Vascular disorders	0/56	1/50
Pulmonary embolism	Vascular disorders	1/56	0/50

Other adverse events by term

Term	Organ system	Sham Control Arm	Treatment Arm:
Oedema peripheral	General disorders	3/56	1/50
Nasopharyngitis	Infections and infestations	4/56	2/50
Post procedural haematoma	Injury, poisoning and procedural complications	4/56	6/50
Blood pressure increased	Investigations	3/56	2/50
Glomerular filtration rate decreased	Investigations	5/56	2/50
Back pain	Musculoskeletal and connective tissue disorders	5/56	2/50
Headache	Nervous system disorders	7/56	11/50
Hypertension	Vascular disorders	5/56	3/50
Hypertensive crisis	Vascular disorders	3/56	1/50
Anaemia	Blood and lymphatic system disorders	1/56	0/50
Lymphadenopathy	Blood and lymphatic system disorders	1/56	0/50
Chest discomfort	Cardiac disorders	0/56	1/50
Dyspnoea exertional	Cardiac disorders	0/56	1/50
Palpitations	Cardiac disorders	0/56	1/50
Sinus tachycardia	Cardiac disorders	1/56	0/50
Tachycardia	Cardiac disorders	2/56	1/50
Ocular discomfort	Eye disorders	0/56	1/50
Abdominal discomfort	Gastrointestinal disorders	0/56	2/50
Abdominal pain	Gastrointestinal disorders	1/56	1/50
Coeliac artery compression syndrome	Gastrointestinal disorders	1/56	0/50
Dyspepsia	Gastrointestinal disorders	1/56	0/50
Gastroenteritis viral	Gastrointestinal disorders	1/56	0/50
Haemorrhoids	Gastrointestinal disorders	1/56	0/50
Haemorrhoids thrombosed	Gastrointestinal disorders	1/56	0/50
Adverse drug reaction	General disorders	0/56	1/50
Asthenia	General disorders	1/56	0/50
Chest pain	General disorders	0/56	1/50
Drug intolerance	General disorders	0/56	1/50
Non-cardiac chest pain	General disorders	0/56	1/50
Oedema	General disorders	1/56	0/50
Oedema peripheral	General disorders	1/56	3/50
Peripheral swelling	General disorders	0/56	1/50
Puncture site haematoma	General disorders	0/56	1/50
Puncture site haemorrhage	General disorders	0/56	1/50
Cholelithiasis	Hepatobiliary disorders	0/56	1/50
Abdominal abscess	Infections and infestations	0/56	1/50
Acute sinusitis	Infections and infestations	1/56	0/50
Appendicitis perforated	Infections and infestations	0/56	1/50
Asymptomatic COVID-19	Infections and infestations	1/56	1/50
COVID-19	Infections and infestations	2/56	1/50
Diverticulitis	Infections and infestations	1/56	0/50
Pharyngitis	Infections and infestations	0/56	1/50
Sinusitis	Injury, poisoning and procedural complications	1/56	0/50
Upper respiratory tract infection	Injury, poisoning and procedural complications	1/56	0/50
Urinary tract infection	Infections and infestations	0/56	1/50
Arterial intramural haematoma	Injury, poisoning and procedural complications	0/56	1/50
Head injury	Injury, poisoning and procedural complications	0/56	1/50
Joint injury	Injury, poisoning and procedural complications	1/56	0/50
Limb injury	Injury, poisoning and procedural complications	0/56	1/50
Post procedural complication	Injury, poisoning and procedural complications	0/56	1/50
Post procedural haemorrhage	Injury, poisoning and procedural complications	1/56	0/50
Procedural pain	Injury, poisoning and procedural complications	0/56	2/50
Scratch	Injury, poisoning and procedural complications	0/56	1/50
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	1/56	0/50
Blood pressure diastolic increased	Investigations	0/56	1/50
Blood sodium decreased	Investigations	0/56	1/50
Glycosylated haemoglobin increased	Investigations	0/56	1/50
Haemoglobin decreased	Investigations	1/56	0/50
Gout	Metabolism and nutrition disorders	0/56	1/50
Hypercholesterolaemia	Metabolism and nutrition disorders	0/56	1/50

59 more terms not shown.

+Locations (4)

Facility	City	Country
Cliniques Universitaires Saint-Luc	Brussels	Belgium
Clinique Pasteur Toulouse	Toulouse	France
Universitätsklinikum des Saarlandes	Homburg/Saar	Germany
NIHR Barts Cardiovascular Biomedical Research Unit	London	United Kingdom

+Publications

Pathak A, Rudolph UM, Saxena M, Zeller T, Muller-Ehmsen J, Lipsic E, Schmieder RE, Sievert H, Halbach M, Sharif F, Parise H, Fischell TA, Weber MA, Kandzari DE, Mahfoud F. Alcohol-mediated renal denervation in patients with hypertension in the absence of antihypertensive medications. EuroIntervention. 2023 Sep 18;19(7):602-611. doi: 10.4244/EIJ-D-23-00088. PMID 37427416
Results publication: Bytyqi V, Kannenkeril D, Striepe K, Bosch A, Karg MV, Schmid A, Schiffer M, Uder M, Schmieder RE. Predicting blood pressure response to renal denervation based on a new approach. J Hypertens. 2025 Mar 1;43(3):413-419. doi: 10.1097/HJH.0000000000003918. Epub 2024 Oct 29. PMID 39526682
Results publication: Bertog S, Sharma A, Mahfoud F, Pathak A, Schmieder RE, Sievert K, Papademetriou V, Weber MA, Haratani N, Lobo MD, Saxena M, Kandzari DE, Fischell TA, Sievert H. Alcohol-Mediated Renal Sympathetic Neurolysis for the Treatment of Hypertension: The Peregrine Infusion Catheter. Cardiovasc Revasc Med. 2021 Mar;24:77-86. doi: 10.1016/j.carrev.2020.09.003. Epub 2020 Sep 7. PMID 32958438

+Study documents

Study Protocol (PDF, 2021-12-14)
Statistical Analysis Plan (PDF, 2021-11-19)

+Investigators

Felix Mahfoud, Prof.Dr.med., Principal investigator, Universitätsklinikum des Saarlandes Klinik für Innere Medizin III Kardiologie, Angiologie und Internistische Intensivmedizin, Germany
Atul Pathak, Prof., Principal investigator, Clinique Pasteur Hi-LAB, Toulouse, France

My Notes

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