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First-in-Human Multicenter Study of a Multi-Electrode Renal Denervation Catheter in Patients With Drug-Resistant Hypertension - EnligHTN I
Description:
Results from the SYMPLICITY-1 and -2 trials have demonstrated significant improvements in blood pressure management with percutaneous renal ablation and denervation in patients with resistant hypertension. Ablations in these trials were performed with a proprietary catheter that has a single-tip electrode. The current trial is a phase I trial that sought to investigate the safety and efficacy of a multi-electrode catheter ablation system (EnligHTN) in patients with resistant hypertension.
Hypothesis:
Renal denervation with a multi-electrode catheter ablation system would be safe and efficacious in improving blood pressure control in patients with resistant hypertension.
Study Design
- Randomized
- Blinded
- Parallel
Patient Populations:
- Willing/able to comply with follow-up schedule
- Appropriate renal artery anatomy
- Office SBP ≥160 mm Hg (≥150 mm Hg if diabetes)
- Stable use of ≥3 antihypertensive medications concurrently at maximally tolerated doses for a minimum of 14 days prior to enrollment of which one is a diuretic, or patient was on diuretic previously, but documented to be diuretic intolerant
- ≥18 and ≤80 years old
Number of enrollees: 46
Duration of follow-up: 6 months
Percentage female: 33%
Exclusions:
- Prior renal artery intervention or evidence of renal artery disease (diameter stenosis >30%)
- Multiple main renal arteries in either kidney or main renal arteries <4 mm in diameter or <20 mm in length
- eGFR of <45 ml/min/1.73 m2
- Type 1 diabetes mellitus or identified secondary cause of hypertension
- Hemodynamically significant valvular heart disease
- Chronic atrial fibrillation/atrial flutter
Primary Endpoints:
- Safety: All adverse events
- Efficacy: Reduction in SBP/DBP at 6 months
Secondary Endpoints:
- Change in renal function
Drug/Procedures Used:
Ablation was performed percutaneously via femoral access. The electrode was 8F compatible. An appropriate basket size was chosen (small basket 4.0-5.5 mm diameter/large basket 5.5-8.0 mm diameter). Ablation was performed with the St. Jude Medical EnligHTN renal denervation system. A minimum of four to maximum of eight ablation sites were performed in each main renal artery, with each ablation lasting 90 seconds per electrode. In general, eight ablations were attempted per renal artery to achieve circumferential ablation.
Principal Findings:
A total of 46 patients underwent renal denervation. The median procedure time (from initiation to completion of radiofrequency energy delivery) was 34.0 minutes. The mean body mass index was 32 kg/m2, and mean estimated glomerular filtration rate (eGFR) was 87 ml/min. The mean number of antihypertensive medications at baseline was 4.1. Baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) was 176/96 mm Hg.
Safety: There were no serious periprocedural events including renal artery dissections, new stenosis, or major vascular access complications. Vasospasm developed in 12 patients, but none were ≥50% (flow-limiting). One patient each developed worsening proteinuria, symptomatic hypotension, and worsening of pre-existing renal artery stenosis over 6 months of follow-up. No patients were noted to have a significant change in renal function. Mean eGFR at 1 and 6 months were 85 and 82 ml/min, respectively.
Efficacy: Mean SBP/DBP declined to 148/87 mm Hg and 150/86 mm Hg at months 1 and 6, respectively. This corresponded to mean reduction in SBP/DBP of 28/10 mm Hg and 26/10 mm Hg at months 1 and 6 compared with baseline, respectively (p < 0.0001 for both). Similar reductions were noted in 24-hour ambulatory BP from baseline (10/5 and 10/6 at months 1 and 6, respectively). Approximately 80% of patients were considered responders (≥10 mm Hg reduction in BP from baseline). Approximately 41% had SBP <140 mm Hg at month 6 (no longer hypertensive).
18-Month Follow-Up: In addition to the above, one patient developed new renal artery stenosis on follow-up to 18 months. Mean eGFR at 12 and 18 months was 86 and 77 ml/min, respectively. The effects of ablation appeared to be enduring: mean reduction in SBP/DBP were 27/11 mm Hg and 24/10 mm Hg at months 12 and 18 compared with baseline, respectively (p < 0.0001 for both). Approximately 77% of patients were considered responders at 18 months (≥10 mm Hg reduction in BP from baseline).
Interpretation:
The results of the phase I EnligHTN I trial indicate that renal denervation with the multi-electrode EnligHTN ablation system is safe and efficacious in reducing SBP and DBP at 18 months in patients with drug-resistant hypertension (baseline use of 4.1 antihypertensive medications). In this small study, overall response rate was 76%. No major adverse events were noted at 18 months of follow-up. These results are very exciting and similar to those noted in the single-electrode based SYMPLICITY-1 and 2 trials. The benefit of multiple electrodes is mainly reduced total ablation time. Longer-term follow-up, and larger trials are eagerly awaited. Numerous other renal denervation systems are also being actively studied.
References:
Presented by Dr. Stephen G. Worthley at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2013), San Francisco, CA, October 28, 2013.
Worthley SG, Tsioufis CP, Worthley MI, et al. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J 2013;Jun 19:[Epub ahead of print].
Presented by Dr. Vasilios Papademetriou at American Heart Association Scientific Sessions, Los Angeles, CA, November 5, 2012.
Keywords: Electrodes, Denervation, Diuretics, Hypotension, Blood Pressure, Proteinuria, Constriction, Pathologic, Renal Artery Obstruction, Body Mass Index, Glomerular Filtration Rate, Catheter Ablation, Hypertension, Diabetes Mellitus
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