Sacubitril/Valsartan Treats Patients With Essential Hypertension and Type 2 Diabetic Nephropathy

NCT ID: NCT06501651

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 297 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2025-04-10

Brief Summary

This study aims to compare the efficacy and safety of Sacubitril/Valsartan versus Valsartan in patients with essential hypertension and type 2 diabetic nephropathy over a 12-week treatment period, including two treatment groups, with a total of 297 eligible subjects randomly assigned in a 2:1 ratio to either the experimental group or the control group.Subjects will participate in the study through two phases: the screening period and the follow-up period.The primary outcome measure is the change in systolic blood pressure from baseline after 12 weeks of treatment.

Conditions

Essential Hypertension; Type 2 Diabetes; Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Initial Dose: The starting dose of Sacubitril/Valsartan is 200 mg once daily. Dose Adjustment: If blood pressure targets (SBP < 130 mmHg and DBP < 80 mmHg) are not achieved after 2 weeks of treatment, the dose of Sacubitril/Valsartan should be doubled to 400 mg once daily.

Additional Treatment: If blood pressure targets are still not met after an additional 2 weeks of treatment, Nifedipine controlled-release tablets (30 mg once daily) should be added to the regimen.

Group Type: EXPERIMENTAL

Sacubitril/Valsartan

Intervention Type: DRUG

Sacubitril/Valsartan is a novel antihypertensive medication composed of an angiotensin II receptor blocker (ARB) Valsartan and a neprilysin inhibitor Sacubitril in a 1:1 molar co-crystal form. Sacubitril is a prodrug that, once ingested, is metabolized by esterases into its active form, which inhibits neprilysin activity. Neprilysin has various substrates, including natriuretic peptides and angiotensin II (Ang II). By inhibiting neprilysin, the levels of natriuretic peptides that have antihypertensive and organ-protective effects are increased. The other component, Valsartan, effectively inhibits the Ang II type 1 receptor (AT1R), providing additional antihypertensive and organ-protective effects. The co-crystal structure ensures that Sacubitril and Valsartan have similar absorption and elimination rates, thereby synchronizing their pharmacological effects.

Comparator

Initial Dose: The starting dose of Valsartan is 80 mg once daily. Dose Adjustment: If blood pressure targets (SBP < 130 mmHg and DBP < 80 mmHg) are not achieved after 2 weeks of treatment, the dose of Valsartan should be doubled to 160 mg once daily.

Additional Treatment: If blood pressure targets are still not met after an additional 2 weeks of treatment, Nifedipine controlled-release tablets (30 mg once daily) should be added to the regimen.

Group Type: ACTIVE_COMPARATOR

Valsartan

Intervention Type: DRUG

Valsartan, effectively inhibits the Ang II type 1 receptor (AT1R), providing both antihypertensive and organ-protective effects.

Interventions

Sacubitril/Valsartan

Sacubitril/Valsartan is a novel antihypertensive medication composed of an angiotensin II receptor blocker (ARB) Valsartan and a neprilysin inhibitor Sacubitril in a 1:1 molar co-crystal form. Sacubitril is a prodrug that, once ingested, is metabolized by esterases into its active form, which inhibits neprilysin activity. Neprilysin has various substrates, including natriuretic peptides and angiotensin II (Ang II). By inhibiting neprilysin, the levels of natriuretic peptides that have antihypertensive and organ-protective effects are increased. The other component, Valsartan, effectively inhibits the Ang II type 1 receptor (AT1R), providing additional antihypertensive and organ-protective effects. The co-crystal structure ensures that Sacubitril and Valsartan have similar absorption and elimination rates, thereby synchronizing their pharmacological effects.

Intervention Type: DRUG

Valsartan

Valsartan, effectively inhibits the Ang II type 1 receptor (AT1R), providing both antihypertensive and organ-protective effects.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 years or older, no gender restriction;
• Diagnosed with mild to moderate primary hypertension (140 ≤ SBP < 180 mmHg and/or 90 ≤ DBP < 110 mmHg), including newly diagnosed or inadequately treated patients (those who have not followed previous medical advice and have uncontrolled blood pressure according to the investigator);
• Diagnosed with type 2 diabetes (according to Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)), and meeting the following conditions: a) Continuously on ≥ 1 glucose control medication regimens (which may include long-acting insulin) for at least 12 weeks before screening, with a stable treatment regimen (i.e., the same medication and dosage) for at least 28 days before screening, and maintaining this regimen during the study. At the investigator's discretion, the dose of supplemental short-acting insulin can be adjusted as needed to achieve adequate glucose control; b) HbA1c level ≤ 10.5% and fasting (≥ 8 hours) plasma glucose level ≤ 13.3 mmol/L (if fasting glucose > 13.3 mmol/L, the investigator may repeat the test to determine eligibility);
• Urine albumin/creatinine ratio (UACR) ≥ 30 mg/g in two measurements taken on separate days or eGFR < 60 mL/min/1.73 m²;
• Non-pregnant or fertile patients (male or female) using reliable contraception;
• Female patients with potential for pregnancy must have a negative pregnancy test at screening;
• Subjects must voluntarily agree to comply strictly with the study protocol requirements and sign a written informed consent form.

Exclusion Criteria

• Presence of severe hypertension, malignant hypertension, hypertensive emergencies, or hypertensive crises;
• History or evidence of secondary hypertension within 12 months before screening, including but not limited to any of the following: renovascular hypertension, renal parenchymal hypertension, unilateral or bilateral renal artery stenosis, coarctation of the aorta, primary aldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension;
• History of angioedema (drug-related or other causes) within 12 months before screening;
• Presence of diabetic ketoacidosis;
• History or evidence of secondary diabetes within 12 months before screening, including but not limited to any of the following: endocrine disorders causing carbohydrate metabolism disorders, pancreatogenic diabetes, hepatogenic diabetes, nephrogenic diabetes, etc.;
• History of malignancy in any organ system (excluding localized basal cell carcinoma of the skin);
• History of acute stroke, lacunar infarction, or dementia within 6 months before screening;
• History of coronary artery bypass graft surgery or any percutaneous coronary intervention (PCI) within 6 months before screening;
• Previously diagnosed or currently diagnosed heart failure (NYHA Class III-IV) or clinically significant valvular heart disease;
• History or current diagnosis of cardiac abnormalities: (1) second or third-degree atrioventricular block without a pacemaker; (2) clinically significant arrhythmias, including atrial fibrillation with a ventricular rate ≥ 120 bpm; (3) family history of long QT syndrome or torsades de pointes ventricular tachycardia;
• Chronic kidney disease stage 4 or higher (eGFR < 30 mL/min/1.73 m²), receiving renal dialysis, or history of kidney transplantation;
• Significant abnormalities in laboratory tests, such as potassium levels > 5.5 mmol/L or < 3.5 mmol/L, sodium levels < 130 mmol/L, liver function (ALT, AST) results > 3 times the upper limit of normal;
• History of allergy to antihypertensive drugs such as ARBs, Angiotensin-Converting Enzyme (ACE) inhibitors, or renin inhibitors;
• Clear history of intolerance to drugs similar to the study medication (e.g., ACE inhibitors, ARBs);
• Use of traditional Chinese or Western medicines that could affect the study's efficacy during the study period (see appendix for list);
• Any surgery or medical condition that significantly alters the absorption, distribution, metabolism, or excretion of any medication, including but not limited to the following: clinically significant gastrointestinal surgery within 12 months before the screening (e.g., gastrectomy, gastrointestinal anastomosis, bowel resection, gastric bypass, gastroenterostomy, or gastric banding), current active inflammatory bowel disease or history of active inflammatory bowel disease;
• Pregnant or breastfeeding women, or patients of childbearing potential unwilling or unable to use effective contraception during the study period;
• Participation in another clinical study using any investigational drug or observational study within 30 days before screening;
• Other conditions that, in the investigator's judgment, may affect the conduct of the clinical study or the determination of study results.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Second Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

Nanchong Central Hospital

OTHER_GOV

Sponsor Role: collaborator

The People's Hospital of Leshan

OTHER

Sponsor Role: collaborator

The Affiliated Traditional Chinese Medicine Hospital Of Southwest Medical University

UNKNOWN

Sponsor Role: collaborator

Chengdu First People's Hospital

OTHER

Sponsor Role: collaborator

Mianyang People's Hospital

UNKNOWN

Sponsor Role: collaborator

Guan'an People's Hospital

UNKNOWN

Sponsor Role: collaborator

Meishan Traditional Chinese Medicine Hospital

OTHER

Sponsor Role: collaborator

Qijiang District People's Hospital

UNKNOWN

Sponsor Role: collaborator

Meishan People's Hospital

UNKNOWN

Sponsor Role: collaborator

The First People's Hospital of Guangyuan

UNKNOWN

Sponsor Role: collaborator

Dazhou Central Hospital

OTHER

Sponsor Role: collaborator

Sichuan Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

tianwenjie1976

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital

Chengdu, Sichuan, China

Countries

China

Central Contacts

Wenjie Tian Chief Physician

Role: CONTACT

tianwenjie1976@hotmail.com

086-17708130310

Facility Contacts

Hospital Operator

Role: primary

syyirb@163.com

086-028-87393401

Other Identifiers

Ethical Review 2024(15-1)

Identifier Type: -

Identifier Source: org_study_id