Sacubitril/Allisartan for Hypertensive Patients With Overweight or Obesity (SHOT)

Sacubitril/Allisartan Versus Amlodipine for Hypertensive Patients With Overweight or Obesity: A Multicenter, Open-Label, Randomized Controlled Trial

To compare the efficacy and safety of sacubitril/Allisartan versus amlodipine in the antihypertensive treatment of overweight/obese patients with primary hypertension

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension
• Intervention / Treatment: Drug: sacubitril/allisartan; Drug: Amlodipine

Detailed Description

This study is a prospective, randomized, controlled, open-label trial conducted in overweight/obese patients with primary mild-to-moderate hypertension, aiming to compare the efficacy and safety of sacubitril/Allisartan versus amlodipine treatment.

The study consists of two phases: a washout period (maximum 2 weeks, for patients currently receiving antihypertensive medication) and a treatment period (8 weeks). Patients already on antihypertensive therapy must complete a 2-week washout period (i.e., discontinue antihypertensive treatment), while those with no prior history of antihypertensive medication use are exempt from the washout.

All patients undergo eligibility assessment against inclusion and exclusion criteria before randomization. Eligible patients are randomly assigned in a 1:1 ratio to sacubitril/Allisartan group or Amlodipine group. In sacubitril/Allisartan group, oral administration of sacubitril/Allisartan 240mg once daily for 4 consecutive weeks. If blood pressure reaches the target, the original regimen is continued; otherwise, the dose of sacubitril/Allisartan is increased to 480mg once daily for another 4 weeks of treatment. In Amlodipine group, oral administration of amlodipine 5mg once daily for 4 consecutive weeks. If blood pressure reaches the target, the original regimen is continued; otherwise, the dose of amlodipine is increased to 10mg once daily for another 4 weeks of treatment.

The total treatment period is 8 weeks of oral medication. Patients will attend study visits on the day before treatment initiation (Day 0), at the end of Week 4, and at the end of Week 8 of the treatment period for efficacy and safety assessments, respectively.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Liu, MD; Phone Number: +8610 88325457; Email: heartcenter@163.com

Study Locations

• China
  • Beijing, China
    • Peking University People's Hospital
    • Contact: Jing Liu; Phone Number: +8610 88325457; Email: heartcenter@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 18 and 75 years inclusive, regardless of gender;
2. Body Mass Index (BMI) ≥ 24 kg/m²;
3. Diagnosed with essential hypertension, either untreated or currently receiving antihypertensive medication;
4. For patients who have not received antihypertensive medication in the past 3 months, the msSBP at the screening visit must be ≥ 150 mmHg and < 180 mmHg;
5. For patients currently receiving antihypertensive medication, the msSBP at the screening visit must be ≥ 140 mmHg and < 180 mmHg; and at the visit after the washout period, the msSBP must be ≥ 150 mmHg and < 180 mmHg.

Exclusion Criteria:

1. Severe hypertension (msSBP ≥ 180 mmHg and/or msDBP ≥ 110 mmHg); malignant hypertension, etc.;
2. History of or diagnostic evidence for obstructive sleep apnea (OSA);
3. History of angioedema;
4. History of or diagnostic evidence for secondary hypertension;
5. Hypertension complicated with the following conditions: acute coronary syndrome, myocardial infarction, percutaneous coronary intervention, or stroke occurring within 12 months; New York Heart Association (NYHA) Class II-IV heart failure, large aortic aneurysm or aortic dissection, atrioventricular block of degree II or higher, sick sinus syndrome, bradycardia (heart rate < 50 beats per minute) or other arrhythmias requiring antiarrhythmic drugs, as well as severe diseases such as epilepsy and syncope;
6. Clinically significant abnormalities in laboratory tests (serum potassium > 5.5 mmol/L or < 3.5 mmol/L; serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2.5 × upper limit of normal (ULN); serum creatinine > 1.5 × ULN);
7. Type 1 diabetes mellitus and type 2 diabetes mellitus with poor glycemic control (glycated hemoglobin (HbA1c) > 8.0%);
8. Patients currently using drugs with weight-loss effects such as glucagon-like peptide-1 (GLP-1) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors;
9. Patients undergoing hemodialysis or strict salt-restriction therapy;
10. Known or suspected allergy to sacubitril/allisartan, sacubitril/valsartan sodium, amlodipine, or related drugs;
11. Patients deemed unsuitable for participation in the study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amlodipine	Drug: Amlodipine; Amlodipine group: Oral administration of amlodipine 5mg once daily for 4 consecutive weeks. If blood pressure reaches the target, the original regimen is continued; otherwise, the dose of amlodipine is increased to 10mg once daily for another 4 weeks of treatment; Other Names: CCB; calcium channel blocker
Experimental: Sacubitril/Allisartan	Drug: sacubitril/allisartan; Oral administration of sacubitril/allisartan 240mg once daily for 4 consecutive weeks. If blood pressure reaches the target, the original regimen is continued; otherwise, the dose of sacubitril/valsartan is increased to 480mg once daily for another 4 weeks of treatment; Other Names: ARNI; angiotensin receptor neprilysin inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change in the mean sitting systolic blood pressure (msSBP) from baseline to week 8, assessed for sacubitril/allisartan as compared to amlodipine	From the start of randomization to the end of treatment at 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in the mean sitting diastolic blood pressure (msSBP) from baseline to week 8, assessed for sacubitril/allisartan as compared to amlodipine		From the start of randomization to the end of treatment at 8 weeks
The BP control rate of sacubitril/allisartan compared to amlodipine	BP control was defined as msSBP/msDBP < 140/90mmHg	From the start of randomization to the end of treatment at 4 weeks and 8 weeks
The BP response rate of sacubitril/allisartan compared to amlodipine	The percentage of patients who had a successful response after treatment for msSBP (<140 mmHg or a reduction by ≥20 mmHg from baseline) and msDBP (<90 mmHg or a reduction by ≥10 mmHg from baseline)	From the start of randomization to the end of treatment at 8 weeks
Changes in 24-hour mean ambulatory systolic and diastolic blood pressures of sacubitril/allisartan compared to amlodipine		From the start of randomization to the end of treatment at 8 weeks
Changes in daytime and night-time mean ambulatory blood pressures of sacubitril/allisartan compared to amlodipine		From the start of randomization to the end of treatment at 8 weeks
Changes in circadian rhythm of blood pressure between sacubitril/allisartan compared to amlodipine		From the start of randomization to the end of treatment at 8 weeks
Safety assessments between sacubitril/allisartan compared to amlodipine	Number of participants with adverse events (AEs), serious AEs (SAE), adverse drug reactions (ADR), with abnormal vital signs, abnormal physical exam findings, abnormal laboratory tests results	From the start of randomization to the end of treatment at 8 weeks

Collaborators and Investigators

• Sponsor: Jing Liu
• Investigators: Principal Investigator: Jing Liu, MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 13, 2025
• First Submitted That Met QC Criteria: November 16, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: obesity; overweight; hypertension; sacubitril/Allisartan
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Hypertension; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Cardiovascular Agents; Dihydropyridines; Amlodipine; Calcium Channel Blockers; sacubitril
• Other Study ID Numbers: 2025PHB414

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No