Enalapril Folic Acid Tablets Combined With CCB or Diuretic to Prevent Stroke in Patients With Type H Hypertension

Randomized Controlled Blind End Point Study of Enalapril Folic Acid Tablets Combined With Calcium Antagonist or Diuretic to Prevent Stroke in Patients With Type H Hypertension

Hypertension is a common condition that can cause serious events such as stroke, coronary heart disease and heart failure. Homocysteine (Hcy) is a substance in the body that is harmful to blood vessels. Hyperhomocysteinemia (plasma Hcy≥10 mol/L), which is associated with hypertension, significantly increases the risk of stroke. This type of high blood pressure is called type "H" hypertension. Enalapril folic acid tablet is an innovative drug developed independently in China and is the first choice for the treatment of H type hypertension. Patients with type H hypertension should be treated with enalapril folic acid tablets to reduce stroke.

However, some patients had poor blood pressure control after monotherapy. At this time, other antihypertensive drugs should be used in combination. Amlodipine and Hydrochlorothiazide are the most commonly used and the best combination.

The purpose of this study was to observe the difference in the efficacy of enalapril folic acid tablets in patients with uncontrolled blood pressure who were well tolerated and randomized to aminoclodipine or hydrochlorothiazide in reducing stroke and other cardiovascular and cerebrovascular events, and to explore the relationship between various alternative measures and efficacy.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Enalapril Folic Acid Tablets Combined With amlodipine; Drug: Enalapril Folic Acid Tablets Combined With hydrochlorothiazide

• Study Type: Interventional
• Enrollment (Actual): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1.40-75 years old (inclusive);
• 2. Patients who have been diagnosed with all types of essential hypertension (those who are currently taking antihypertensive drugs with normal blood pressure can still be admitted) or those whose blood pressure screening meets the inclusion criteria;
• 3. Plasma (or serum) Hcy 10 mol/L;
• 4. Enalapril folic acid tablet 10.8 mg/day alone is not up to standard;
• 5. In the case of women of reproductive age, agree to use a reliable method of contraception during the trial;
• 6. Participate voluntarily and sign the informed consent;

Exclusion Criteria:

• 1. Previous stroke with definite diagnosis;
• 2. Patients with previous well-diagnosed myocardial infarction;
• 3. The presence of well-diagnosed heart failure;
• 4. Postoperative revascularization;
• 5.DBP >=110 mmHg or SBP >=180 mmHg;
• 6. Confirmed secondary hypertension;
• 7. Severe physical and systemic disease, which is estimated to be unable to complete the follow-up;
• 8. People with known congenital or acquired organic heart disease;
• 9. People who have had obvious intolerable adverse reactions to ACEI drugs in the past;
• 10. Have contraindications to ACEI drugs (including renal failure) or are allergic to the drugs used in the study or other ingredients in the drugs;
• 11. According to the researchers, there are contraindications to the use of folic acid;
• 12. Pregnant and lactating women;
• 13. If there are other obvious laboratory tests, abnormal physical signs and clinical diseases, it is not suitable to participate in the study according to the researcher's judgment;
• 14. Unwilling to participate in the trial, unwilling or unable to change the existing medication regimen;
• 15. Long-term use of folic acid or health medicines containing folic acid;
• 16.Severe mental disorder, unable to express their will

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
Experimental: Enalapril Folic Acid Tablets Combined With amlodipine; Enalapril Folic Acid Tablets 10.8mg Combined With amlodipine 5 or 10mg	Drug: Enalapril Folic Acid Tablets Combined With amlodipine; Enalapril Folic Acid Tablets 10.8mg Combined With amlodipine 5 or 10mg
Active Comparator: Enalapril Folic Acid Tablets Combined With hydrochlorothiazide; Enalapril Folic Acid Tablets 10.8mg Combined With hydrochlorothiazide 12.5 or 25mg	Drug: Enalapril Folic Acid Tablets Combined With hydrochlorothiazide; Enalapril Folic Acid Tablets 10.8mg Combined With hydrochlorothiazide 12.5 or 25mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stroke rate	Until 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of combined end points of cardiovascular events	Including cardiogenic death, cerebrovascular death, non-fatal stroke, and myocardial infarction	Until 5 years
Rate of all causes of death	Including all causes and unexplained deaths	Until 5 years
Rate of first or recurrent ischemic stroke		Until 5 years
Rate of first or recurrent hemorrhagic stroke		Until 5 years
Rate of myocardial infarction		Until 5 years

Other Outcome Measures

Outcome Measure	Time Frame
Rate of heart failure (hospitalization)	Until 5 years
Rate of coronary revascularization	Until 5 years
Rate of peripheral arterial revascularization	Until 5 years
Rate of malignant tumor	Until 5 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: National Clinical Research Center, Southern Medical University; Ningbo Yinzhou Community Health Service Center
• Investigators: Study Chair: Jian-an Wang, Second Affiliated Hospital of Zhejiang University, School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: June 20, 2021
• First Submitted That Met QC Criteria: June 27, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Natriuretic Agents; Micronutrients; Membrane Transport Modulators; Diuretics; Vitamins; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Hematinics; Angiotensin-Converting Enzyme Inhibitors; Sodium Chloride Symporter Inhibitors; Amlodipine; Enalaprilat; Enalapril; Folic Acid; Vitamin B Complex; Hydrochlorothiazide
• Other Study ID Numbers: 2014-132

Drug and device information, study documents

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