Clinical trial NCT06500689: To Assess Allisartan Isoproxil/Sustained-Release Indapamide in Patients With Essential Hypertension Uncontrolled With Allisartan Isoproxil
Official title: Efficacy and Safety of Allisartan Isoproxil/Sustained-Release Indapamide in Patients With Essential Hypertension Uncontrolled With Allisartan Isoproxil: A Phase III, Multicenter, Randomized, Double-blind, Parallel-controlled, 52-week Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Hypertension
Keywords: Allisartan isoproxil
Indapamide
Essential hypertension
Systolic BP
Diastolic BP
Lead sponsor: Shenzhen Salubris Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-07-15
Enrollment: 366
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: The main objective of the study will be to assess the efficacy and safety of Allisartan Isoproxil/sustained-release indapamide (240 mg/1.5 mg) in patients with mild to moderate essential hypertension uncontrolled after 4-week treatment with Allisartan Isoproxil (240 mg).

Detailed description: Allisartan isoproxil is a novel angiotensin receptor blocke available in China for over ten years and has the same active compound EXP3174 with losartan, while sustained-release indapamide is a long-standing thiazide-type diuretic. The novel single-pill combination of allisartan isoproxil and sustained-release indapamide exerts synergistic antihypertensive effects.

Eligibility criteria: Key Inclusion Criteria:

1. Patients 18-75 years old with mild to moderate essential hypertension;
2. Patients who meet one of the following criteria when screening:

   1. Untreated patients (either newly diagnosed essential hypertension or those patients with a history of hypertension but have not been taking any antihypertensive drugs for at least 2 weeks before the first visit) must have an office msSBP ≥ 150 mmHg and \< 180 mmHg and msDBP\<110 mmHg;
   2. Patients who had not received regular treatment with allisartan isoproxil (240 mg/day) (less than 4 weeks of medication intake or a history of missing doses for 5 or more days within the 4 weeks before screening) with the msSBP of 140 mmHg≤ SBP \<180 mmHg and DBP\<110 mmHg;
   3. Patients currently receiving other antihypertensive agents (non-study medications for at least 2 weeks prior to screening) with the msSBP of 140 mmHg≤ SBP \<180 mmHg and DBP\<110 mmHg, and the clinician determined that it was appropriate to switch to allisartan isoproxil (240 mg/day);
   4. Patients who have been stably treated with allisartan isoproxil (240 mg/day) for at least 4 weeks with the msSBP of 140 mmHg≤ SBP \<180 mmHg and DBP\<110 mmHg.
3. During randomization for the double-blind treatment period, msSBP should be 140 mmHg≤ SBP \<180 mmHg and DBP\<110 mmHg;
4. Participants enrolled in the ABPM study should have 24-hour mean ambulatory blood pressure ≥130/80 mmHg after 4 weeks of monotherapy treatment;
5. Patients who understand and sign the informed consent form.

Key Exclusion Criteria:

1. Patients with secondary hypertension;
2. Patients with msSBP ≥180 m mHg and/or msDBP≥110 mmHg, or withhypertensive emergency or hypertensive urgency.
3. Patients who have taken three or more antihypertensive drugs (including single-pill combination) simultaneously within one month prior to screening.
4. Patients with history of heart failure (New York Heart Association (NYHA) Functional Classification class III and IV), acute coronary syndrome, percutaneous coronary intervention, or other serious heart diseases (such as cardiogenic shock, moderate or severe heart valvular disorders, atrioventricular block second or third degree, bradycardia (with a heart rate \<50 beats per minute), severe arrhythmias) in the past 6 months.
5. Patients with history of severe cerebrovascular diseases (such as hypertensive encephalopathy, cerebrovascular injury, stroke, transient ischemic attack) in the past 6 months.
6. Patients with aortic aneurysm, aortic dissection, or dissecting aneurysm.
7. Patients with severe renal insufficiency (Cr\>1.5 times the upper limit of normal).
8. Patients with hypokalemia or hyperkalemia.

Primary outcomes:
measure: Change from baseline in mean seated systolic blood pressure (msSBP) after 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 12.
Secondary outcomes:
measure: Change from baseline in mean seated systolic blood pressure (msSBP) after 4 and 8 weeks of randomized, double-blind treatment
timeFrame: week 1, week 4, week 8.
measure: Change from baseline in mean seated diastolic blood pressure (msDBP) after 4, 8, and 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 4, week 8, week 12.
measure: The proportion of responders to antihypertensive treatment after 12 weeks of randomized, double-blind treatment. (Responders are the participants achieving SBP/DBP<140/90 mmHg or a reduction from baseline of >20 mmHg in msSBP and/or >10 mmHg in msDBP. )
timeFrame: week 1, week 12.
measure: The proportion of patients meeting the mean sitting blood pressure target (SBP/DBP <140/90mmHg) after 4, 8, and 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 4, week 8, week 12.
measure: The proportion of patients with the mean sitting blood pressure SBP/DBP <130/80mmHg) after 4, 8, and 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 4, week 8, week 12.
measure: Change from baseline in msSBP after 20, 28, 40, and 52 weeks of treatment
timeFrame: week 1, week 20, week 28, week 40, week 52.
measure: Change from baseline in msDBP after 20, 28, 40, and 52 weeks of treatment
timeFrame: week 1, week 20, week 28, week 40, week 52.
measure: The proportion of patients meeting the mean sitting blood pressure target (SBP/DBP <140/90mmHg) after 52 weeks of treatment
timeFrame: week 1, week 52.
measure: The proportion of patients with the mean sitting blood pressure SBP/DBP <130/80mmHg) after 52 weeks of treatment
timeFrame: week 1, week 52.
Other outcomes:
measure: Change from baseline in 24-hour mean systolic and diastolic blood pressure during ambulatory blood pressure monitoring (ABPM) after 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 12.
measure: Change from baseline in daytime mean systolic and diastolic blood pressure during ambulatory blood pressure monitoring (ABPM) after 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 12.
measure: Change from baseline in nighttime mean systolic and diastolic blood pressure during ambulatory blood pressure monitoring (ABPM) after 12 weeks of randomized, double-blind treatment
timeFrame: week 1, week 12.
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Xuancheng
country: China
facility: Xuancheng People's Hospital
state: Anhui
city: Beijing
country: China
facility: Aerospace Central Hospital
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Affiliated Three Gorges Hospital
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial People's Hospital
state: Gansu
city: Foshan
country: China
facility: Shunde Hospital of Southern Medical University
state: Guangdong
city: Zhanjiang
country: China
facility: Guangdong Medical University Affiliated Hospital
state: Guangdong
city: Nanning
country: China
facility: Nanning First People's Hospital
state: Guangxi
city: Shijiazhuang
country: China
facility: Hebei Provincial People's Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: Shijiazhuang People's Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Daqing
country: China
facility: Daqing People's Hospital
state: Heilongjiang
city: Kaifeng
country: China
facility: Kaifeng Traditional Chinese Medicine Hospital
state: Henan
city: Shiyan
country: China
facility: Chinese Medicine Dongfeng General Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan First Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Fourth Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Sixth Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Second Hospital of Central South University
state: Hunan
city: Yueyang
country: China
facility: Yueyang Central Hospital
state: Hunan
city: Yueyang
country: China
facility: Yueyang People's Hospital
state: Hunan
city: Huai'an
country: China
facility: Huai'an First People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: Suzhou Municipal Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Ganzhou
country: China
facility: Ganzhou People's Hospital
state: Jiangxi
city: Ganzhou
country: China
facility: The First Affiliated Hospital of Gannan Medical College
state: Jiangxi
city: Pingxiang
country: China
facility: Pingxiang People's Hospital
state: Jiangxi
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Nanchong
country: China
facility: Nanchong Central Hospital
state: Sichuan
city: Suining
country: China
facility: Suining Central Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Ningbo
country: China
facility: Li Huili Hospital of Ningbo Medical Center
state: Zhejiang
city: Quzhou
country: China
facility: Quzhou People's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou Medical University Affiliated First Hospital
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital of Fujian Medical University, Fuzhou 350212, China
name: Jinxiu Lin, MD
role: PRINCIPAL_INVESTIGATOR
References: