Clinical trial NCT05545059: Effects and Safety of Sacubitril/Valsartan on Refractory Hypertension
Official title: Effects and Safety of Sacubitril/Valsartan Versus Valsartan on Refractory Hypertension: The EOSORH Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Resistant Hypertension
Keywords: Resistant hypertension
ambulatory blood pressure
sacubitril/valsartan
valsartan
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-09-19
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Resistant hypertension (RH) accounted for a considerable proportion of patients with hypertension. It has been revealed to impose certain adverse effects on the prognosis of patients with cardiovascular diseases. The antihypertensive effect of sacubitril/valsartan being fully confirmed in previous studies, there were no related randomized controlled trials (RCT) about this potency among Chinese patients with RH. The investigators designed this study to evaluated effects and safety of sacubitril/valsartan versus valsartan on Chinese patients with RH.

Detailed description: Background Resistant hypertension (RH) accounted for a considerable proportion of patients with hypertension. It has been revealed to impose certain adverse effects on the prognosis of patients with cardiovascular diseases. The antihypertensive effect of sacubitril/valsartan being fully confirmed in previous studies, there were no related randomized controlled trials (RCT) about this potency among Chinese patients with RH.

Purpose Describing the design of the Effects of Sacubitril/valsartan Versus Valsartan on Refractory Hypertension (EOSORH) trial.

Methods and analysis This is a monocentric, randomized, parallel-group, controlled trial which will investigate the efficacy and safety of sacubitril/valsartan in the treatment of Chinese patients with RH. A total of 138 patients will be enrolled who are diagnosed with RH according to the Guidelines for Prevention and Treatment of Hypertension in China (2018 revision). After a washout period, subjects will be randomized to sacubitril/valsartan group or valsartan group in a 1:1 ratio. The primary outcome is the change in 24 hours average ambulatory systolic blood pressure (SBP) from baseline to 8 weeks after randomization, comparing the sacubitril/valsartan group with valsartan group. The secondary outcomes including change in 24 hours average ambulatory diastolic blood pressure (DBP), clinic blood pressure and series of cardiac and renal hematologic indicators. Safety endpoints will also be evaluated, covered changes in blood potassium level, renal function, hypotension, etc. Full Analysis Set (FAS), per-protocol set (PPS) and safety set (SS) will be defined. Baseline data will be analyzed by using data from FAS whereas the analysis of primary outcome will be based on FAS and PPS but the conclusions of FAS are dominant.

Ethics and dissemination The research protocol has been approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University. This research is designed to investigate the efficacy and safety of sacubitril/valsartan in Chinese RH patients. Findings will be shared by Sun Yat-sen Memorial Hospital, policymakers and the academic community to promote the clinical pharmacal therapy of RH in China.

Discussion The effects of sacubitril/valsartan on hypertension have been widely reported by a series of large RCT in recent years, while its application in RH patients is still elusive. The study will provide a new pharmacal strategy for the treatment of RH.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of resistant hypertension
* ≥18 and ≤75 years old at the time of randomization
* Must agree to comply with all requirements and sign the informed consent form

Exclusion Criteria:

* unwilling to sign informed consent.
* Severe renal insufficiency
* Research related drug contraindications
* secondary hypertension
* Cardiovascular event
* Persistent arrhythmia, valvular heart disease, and class III-IV heart failure or left ventricular ejection fraction \<45%.
* Severe liver function impairment (Child-Pugh C), biliary cirrhosis and/or cholestasis
* History of angioedema and asthma
* Woman of childbearing age who do not take effective contraceptive measures or pregnant or breastfeeding
* Allergic to drugs related to the study
* Suffering from serious tumor-related diseases, receives tumor-related treatment, or has a life expectancy of less than 2 years
* Planning to join other clinical trials
* Anticipated changes in medical conditions
* Need to take study-related drugs for reasons other than hypertension
* Suffering from other diseases that may prevent the patient from participating fully period of the study
* Other any concomitant conditions
* Must continuously take any drugs that affect the results

Primary outcomes:
measure: the change in 24 hours average ambulatory systolic pressure from baseline to 8 weeks after randomization
timeFrame: 8 weeks after randomization
Secondary outcomes:
measure: Change in 24 hours average ambulatory diastolic blood pressure, daytime and night-time blood pressure and office blood pressure
timeFrame: 8 weeks after randomization
measure: Change in level of cardiac marker reflecting the heart failure
timeFrame: 8 weeks after randomization
measure: Change in level of cardiac marker reflecting myocardial damage
timeFrame: 8 weeks after randomization
measure: Change in level of novel cardiac marker reflecting the heart failure
timeFrame: 8 weeks after randomization
measure: Change in level of cardiac marker reflectting myocardial metabolism
timeFrame: 8 weeks after randomization
measure: Change in level of estimated glomerular filtration rate
timeFrame: 8 weeks after randomization
measure: Change in level of urinary albumin to creatinine ratio
timeFrame: 8 weeks after randomization
measure: the control rate of blood pressure
timeFrame: 8 weeks after randomization
measure: Change in left atrium diameter determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in left ventricular mass index determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in left ventricular end diastolic volume index determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in left ventricular end systolic volume index determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in left ventricular ejection fraction determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in E/A determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in E/e' determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in left ventricular overall longitudinal peak strain determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in overall radial peak strain determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in overall circumstantial peak strain determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
measure: Change in area strain determined by ultrasonic cardiogram and three-dimensional speckle tracking imaging
timeFrame: 8 weeks after randomization
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Dengfeng Geng, Dr.
role: PRINCIPAL_INVESTIGATOR
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