Clinical trial NCT02761811: Sympathetic Mapping/ Ablation of Renal Nerves Trial
Official title: A Prospective, Multicenter, Single Blind, Randomized and Sham Controlled Trial of Renal Sympathetic Denervation Using SyMapCath I™ Catheter and SYMPIONEER S1™ Stimulator/Generator for the Treatment of Hypertension (SMART Trial)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hypertension
Lead sponsor: SyMap Medical (Suzhou), Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2016-05-04
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of targeted renal sympathetic denervation using SyMapCath I® and SYMPIONEER S1® Stimulator/ Generator in patients with essential hypertension for at least 6 months of the disease history and pharmacotherapy, however, their blood pressure still cannot be controlled, then after standardized antihypertensive drug therapy (at least two drugs) for at least 28 days, office systolic blood pressure is still ≥ 150mmHg, ≤180mmHg.

Detailed description: This is a prospective, multicenter, single blind, randomized and sham controlled trial, in which patients are diagnosed with essential hypertension with at least six months of the disease history and pharmacotherapy however their blood pressure still cannot be controlled. The patients will be informed, consent and get into a screening process. During the screening period patients will receive a standardized antihypertensive drug treatment for at least 28 days and office systolic blood pressure is still ≥ 150mmHg, ≤180mmHg, and meet the inclusion and exclusion criteria. These patients will conduct renal artery angiography and be allocated to either renal sympathetic nerve denervation group or renal artery angiography group by a randomizing system in a 1:1 ratio (220 patients, 110 pairs). Patients with office systolic blood pressure which is not achieved ideal level (\<140 mmHg) will titrate doses or classes of antihypertensive drugs according to a predefined standardized medication regimen until their office systolic blood pressure \<140 mmHg, whereas in principle patients should follow the drug titration regimen, however, it is allowed to adjust antihypertensive medications per the real-world needs after 12 months.

Physicians who perform post-procedure patient management and physicians who perform renal denervation procedures are blinded to each other.

Patients will be followed at 7 days after the procedure or at discharge from hospital, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, 12months, 24months, 36 months, 48 months and 60 months for blood pressure measurements and antihypertensive medications. Urine samples will be collected for drug tests (LC-MS/MS) to determine drug compliance of a patient by an independent laboratory.

Data collecting/management/statistical analysis and laboratory tests will be done by independent, qualified organizations. Independent DSMB/CEC are formed and responsible for assessments of protocol deviations and natures of SAEs.

Eligibility criteria: Inclusion Criteria:

1. Male and non-pregnant female subjects, 18≤age≤65
2. Essential hypertension
3. Office systolic blood pressure ≥150mmHg and ≤180mmHg; and resting heart rate ≥70 bpm without taking beta blocker(Resting heart rate does not taken into account if beta blocker is taken)
4. Average 24-hour ABPM systolic blood pressure ≥130mmHg, or ABPM systolic blood pressure during daytime ≥ 135mmHg, or ABPM systolic blood pressure during nighttime ≥ 120mmHg
5. History of hypertension is longer than 6 months
6. Patient with poor blood pressure control after 6 months of antihypertensive drug therapy, understands the purpose of this study, and is willing to participate and sign the Informed Consent; then the patient receives standard antihypertensive drug treatment (at least two drugs) for at least 28 days, drug compliance ≥80%, office systolic blood pressure ≥150 mmHg and ≤180 mmHg.
7. Patient is compliant and willing to complete clinical follow-up.

Exclusion Criteria:

1. Renal artery anatomy is unqualified including： (1) diameter \<4mm or treatable length \<25mm， (2) multiple renal arteries and the main renal artery supplies a fraction of the blood flow less than 75%, (3) renal artery stenosis \>50% or any renal artery aneurysms on either side, (4) history of renal artery PTA, including balloon angioplasty and stenting.
2. eGFR \<45mL/min/1.73m2 (MDRD formula)
3. Hospitalized within one year due to hypertensive crisis
4. Average 24-hour systolic blood pressure \<130mmHg and ABPM systolic blood pressure during daytime ≤ 135mmHg, and ABMP systolic blood pressure during nighttime ≤ 120mmHg
5. Pulse pressure \>80mmHg
6. During running in period, using antihypertensive drugs other than standardized antihypertensive drugs
7. Participated other clinical trials including both drug and medical device studies within 3 months from current study
8. Female with pregnant or lactating, or having plans for pregnancy within 1 year
9. Patient with sleep apnea who needs chronic oxygen-breathing or mechanical ventilation support (for example, tracheostomy)
10. Patients previously or currently suffering from following diseases:

(1) essential pulmonary arterial hypertension, (2) type I diabetes, (3) patients with severe cardiac valvular stenosis who have contradictions and cannot rolerant to significantly reduce blood pressure, (4) within half year, patients had myocardial infraction, unstable angina, syncope or cerebrovascular accidents, (5) history of primary aldosteronism, pheochromocytoma, aorta stenosis, hyperthyroidism or hyperparathyreosis, (6) any disease conditions interfering the measurement of blood pressure (for instance, severe peripheral artery diseases, abdominal artery aneurysm, hemorrhagic disorders such as thrombocytopenia, hemophilia and severe anemia), (7) plans to have surgery or cardiovascular interventions within 6 months, (8) alcohol abuse or unknown drug dependence history, (9) neuroticisms such as depression or anxiety disorders, (10) non-compliant patients who are unable to follow the study protocol per physician's requests.

11. Any contradictions to conduct renal artery stimulation and ablation

Primary outcomes:
measure: The control rate of office systolic blood pressure ( SBP<140mmHg)
timeFrame: 6 months after the treatment
measure: Change in the composite index of antihypertensive drugs to reach control of office systolic blood pressure (<140mmHg)
timeFrame: 6 months after the treatments
Secondary outcomes:
measure: Reduction in average 24-hour Ambulatory Blood Pressure Monitoring (ABPM) systolic blood pressure
timeFrame: 6 months
measure: Postoperative reduction in 24-hour ABPM in systolic, diastolic and mean arterial blood pressure
timeFrame: discharge day or 7 days after procedure
measure: Reduction in office blood pressure
timeFrame: 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 24months, 36 months, 48 months and 60 months
measure: Change in composite index of antihypertensive drugs
timeFrame: 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months, 24months, 36 months, 48 months and 60 months
measure: Success rate of the renal interventional therapy procedure
timeFrame: during the procedure
measure: Success rate of clinical treatment
timeFrame: 7 days after the procedure or at the time the patient is discharged from hospital
measure: All-cause death
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months, 24months, 36 months, 48 months and 60 months
measure: Severe renal dysfunction
timeFrame: 6 months, 24months, 36 months, 48 months and 60 months
measure: Rate of renal artery stenosis assessed by CT angiography
timeFrame: 6 months, 24months, 36 months, 48 months and 60 months
measure: AEs, SAEs, and severe cardio-cerebrovascular events
timeFrame: 1 month, 3 months, 6 months, 9 months, 12months, 24months, 36 months, 48 months and 60 months
measure: Reduction in 24-hour ABPM in systolic and diastolic arterial blood pressure
timeFrame: 24, 36, 48, 60 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Afflicted Hospital of Chongqing Medical University
state: Chongqing
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Shijiazhuang
country: China
facility: Norman Bethune International Peace Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital, Fudan University
state: Shanghai
city: Taiyuan
country: China
facility: Taiyuan Central Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin First Center Hospital
state: Tianjin
Study officials:
affiliation: Peking University First Hospital
name: Yong HUO, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang J, Sun N, Ge J, Jiang H, Yin Y, Chen M, Wang Y, Yao C, Yan X, Sobotka PA, Huo Y. Rationale and Design of Sympathetic Mapping/Ablation of Renal Nerves Trial (SMART) for the Treatment of Hypertension: a Prospective, Multicenter, Single-Blind, Randomized and Sham Procedure-Controlled Study. J Cardiovasc Transl Res. 2023 Apr;16(2):358-370. doi: 10.1007/s12265-022-10307-z. Epub 2022 Aug 30.
citation: Wang Y, Wang JW, Wang Y, Yang B, Yinghua Du A, Kong Z, Chen M, Wang J. Monitoring Antihypertensive Medication Adherence by Liquid Chromatography-Tandem Mass Spectrometry: Method Establishment and Clinical Application. J Cardiovasc Pharmacol. 2021 Oct 1;78(4):581-596. doi: 10.1097/FJC.0000000000001105.