Official Title: “Efficacy of Antihypertensive and Plasma Total Homocysteine Lowering Combined Therapy With Enalapril and Folic Acid in Hypertensive Patients:A Multicenter Double Blind Randomized Clinical Trial”

Combinded therapy with folic acid and enalapril may significantly decrease plasma total homocysteine level and had beneficial effect on blood pressure reduction and glycometabolism.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Inclusion Criteria:

1. Age≥18 years and less than 75 years

2. Essential hypertension patients

3. Sedentary systolic blood pressure≥140mmHg and less than 180mmHg, and/or sedentary diastolic blood pressure≥90mmHg and less than 110mmHg

4. Reproductive women agree to take a reliable contraception measure during the trial

5. Written informed consent

Exclusion Criteria:

1. Pregnant women

2. Women within lactateion period

3. Hypersensitive to Angiotensin-Converting Enzyme Inhibitor (ACEI) or folic acid

4. Easily hypersensitiveness

5. Diagnosed secondum hypertension or skeptical secondum hypertension

6. Severe hypertension (sedentary systolic blood pressure greater than or equal to 180 mmHg and/or sedentary diastoleic blood pressure greater than or equal to 110 mmHg)

7. Severe diseases: - Cardiovascular system - Diagnosed cardia insufficiency (New York Health Association [NYHA] III level and higher) - Hypertrophic obstructive cardiomyopathy (HOCM) - Clinical significantly Valvular Disease of the Heart (VDH) - Acute coronary syndrome or coronary artery interventional therapy or coronary artery bypass graft within three months - Severe arrhythmia such as atrial flutter, atrial fibrillation, ventricular arrhythmia above Lown ?, atrioventricular block above II level, etc. - Alimentary system disorders - Active virus hepatitis - Any of alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), Direct Bilirubin (DB) was above 2 times of it's normal value upper limit, albumin (ALB) greater than 30 g/L - Stomach bulk resect and gastrojejunostomy, stomach intestine malabsorption

Urinary system: - Serum creatinine greater than or equal to 200 mmol/L - Diagnosed stenosis of renal artery, solitary kidney - Renal transplantation

Endocrine system: - Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (fasting glucose greater than or equal to 11.1 mmol/L) - Diagnosed and uncontrolled hyperthyrosis

Respiratory system: - Chronic cough nervous or psyche system: - Transient Ischemia Attach (TIA) or stoke within 3 months - Severe peripheral nerve or vegetative nerve functional disturbance - Psyche or nervous system dysfunction - Drugs or alcohol dependence

Others: - Malignant tumor - Malnutrition, haematogenesis dysfunction, etc.

8. Taking other antihypertensive drugs

9. Taking folic acid or other Vitamin B groups

Primary Outcome Measures:

1. Blood pressure of study participants was measured at baseline, 2th week, 4th week, 6th week and at the end of trial

2. Subjects' plasma total homocysteine concentration were measured at baseline, 4th week and at 8th week.

Secondary Outcome Measures:

1. Participants' living habit and life style were collected at baseline with the original questionnaires.

2. A follow up questionnaire was sent out at 2th week, 4th week, 6th week and at the end of the trial.

Intervention(s) in this Clinical Trial

• Drug: enalapril plus folic acid
  • enalapril 10.0 mg daily for 8 weeks (the control group); enalapril 10.0 mg plus folic acid 0.4 mg daily for 8 weeks (Low-dose group); enalapril 10.0 mg plus folic acid 0.8 mg daily for 8 weeks (High-dose group)

Primary Measures

• Blood pressure of study participants was measured at baseline, 2th week, 4th week, 6th week and at the end of trial Subjects' plasma total homocysteine concentration were measured at baseline, 4th week and at 8th week.
  • Time Frame: 8 weeks
    

Secondary Measures

• Participants' living habit and life style were collected at baseline with the original questionnaires. A follow up questionnaire was sent out at 2th week, 4th week, 6th week and at the end of the trial.
  • Time Frame: 8 weeks
    

Inclusion Criteria:

• Age≥18 years and less than 75 years
• Essential hypertension patients
• Sedentary systolic blood pressure≥140mmHg and less than 180mmHg, and/or sedentary diastolic blood pressure≥90mmHg and less than 110mmHg
• Reproductive women agree to take a reliable contraception measure during the trial
• Written informed consent

Exclusion Criteria:

• Pregnant women
• Women within lactateion period
• Hypersensitive to angiotensin-converting enzyme inhibitor (ACEI) or folic acid
• Easily hypersensitiveness
• Diagnosed secondum hypertension or skeptical secondum hypertension
• Severe hypertension (sedentary systolic blood pressure≥180mmHg and/or sedentary diastoleic blood pressure≥110mmHg)

Severe diseases:

• Cardiovascular system:
• Diagnosed cardia insufficiency (NYHAⅢ level and higher)
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Clinical significantly valvular disease of the heart (VDH)
• Acute coronary syndrome or coronary artery interventional therapy or coronary artery bypass graft within three months
• Severe arrhythmia such as atrial flutter, atrial fibrillation, ventricular arrhythmia above Lown Ⅱ, atrioventricular block above Ⅱ level, et al
• Alimentary system:
• Active virus hepatitis
• Any of alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DB) was above 2 times of it's normal value upper limit, albumin (ALB)＞30g/L
• Stomach bulk resect and gastrojejunostomy, stomach intestine malabsorption
• Urinary system:
• Serum creatinine≥200mmol/L
• Diagnosed stenosis of renal artery, solitary kidney
• Renal transplantation
• Endocrine system:
• Type 1 diabetes mellitus or uncontrolled type 2 diabetes mellitus (fasting glucose≥11.1mmol/L)
• Diagnosed and uncontrolled hyperthyrosis
• Respiratory system:
• Chronic cough
• Nervous or psyche system
• Transient ischemia attach (TIA) or stoke within 3 months
• Severe peripheral nerve or vegetative nerve functional disturbance
• Psyche or nervous system dysfunction
• Drugs or alcohol dependence
• Others:
• Malignant tumor, malnutrition, haematogenesis dysfunction, et al
• Taking other antihypertensive drugs
• Taking folic acid or other Vitamin B groups

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 28 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Anhui Medical University

Overall Clinical Trial Officials and Contacts

Ping Liu, Dr. Study Director Peking University First Hopital  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00520247

Study ID Number: 2005L01101

ClinicalTrials.gov Identifier: NCT00520247

Health Authority: China: State Food and Drug Administration