The Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release in Chinese Patients.

Condition(s) targeted: Hypertension

Intervention: Felodipine tablet (Plendil) alone (Drug); Felodipine tablet (Plendil)+Hydrochlorothiazide (Drug); Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK) (Drug); Felodipine tablets (Plendil)+Lisinopril (Zestril) (Drug)

Phase: N/A

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Ningling Sun, PhD, MD, Principal Investigator, Affiliation: Beijing University People's Hospital, Department of Cardiology

The purpose of this study is to evaluate the effects on blood pressure control, pulse wave velocity, as well as safety and tolerability of felodipine single or combine with other drugs in Chinese Hypertension patients.

Official title: A Randomized, Open-label Study to Evaluate the Effects on Blood Pressure Control, Pulse Wave Velocity, as Well as Safety and Tolerability of Felodipine Sustained Release, Alone and in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide, in Chinese Patients With Mild to Moderate Essential Hypertension.

Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Primary outcome: The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 14 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

Secondary outcome:

The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Percentage of Subjects Reaching Blood Pressure Target (Defined as < 140 / 90 mmHg) After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Change From Baseline Among All Randomized Subjects After 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among All Randomized Subjects After 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 4 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target After 8 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 12 Weeks of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Change of Pulse Wave Velocity at 12 Weeks Compare With Baseline Data of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.

The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone.

The Magnitude of Systolic and Diastolic Blood Pressure Changes From Baseline Among the Subjects Who Reached Target at 2 Weeks of Felodipine Sustained Release, Alone

Detailed description: In this study, investigators will choose male and female subjects aged between 35 and 79 years old with mild to moderate essential hypertension. At first 2 weeks, all patients will use felodipine 5mg daily. If the blood pressure dosen't meet the target (140/90mmHg), they will be randomized into metoprolol, lisinopril or hydrochlorothiazide combination groups for another 4 weeks therapy. After that, if the blood pressure has still not met the target, up-titrate the felodipine into 10mg, followed by a 4 weeks therapy. And if the blood pressure is still not met the target after that, up-titrate the combine drugs into maximum dosage. The whole treatment duration is 14 weeks. The primary outcome is to evaluate the percentage of subjects reaching blood pressure target (defined as < 140 / 90 mmHg) after 14 weeks treatment with felodipine sustained release in combination with metoprolol, lisinopril or hydrochlorothiazide.

Minimum age: 35 Years. Maximum age: 79 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Provision of written informed consent 2. Female or male aged between 35-79 years old 3. Mild to moderate essential hypertension patients who meet any of the following criterias:

- Newly diagnosed, drug-naive, or without any antihypertension treatment for at

least 3 months, moderate essential hypertension patients. (160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg)

- Newly diagnosed, drug-naive, or without any antihypertension treatment for at

least 3 months, mild essential hypertension patients (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk (a)(having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus). (a) according to Chinese guideline for prevention and treatment of patients with hypertension 2004.

- The patients have already received starting dosage of single anti-hypertension

drug therapy (exclude the drugs containing felodipine component ), however the blood pressure is not well controlled (140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg). After stopping the drug for 5 eliminating half life time, the patients meet any one of the following two: 1. 160mmHg mean SiSBP 180mmHg or 100mmHg mean SiDBP 110mmHg. 2. 140mmHg mean SiSBP 160mmHg or 90mmHg mean SiDBP 100mmHg) with high or extreme high cardiovascular risk* (having 3 or more than 3 risk factors and/or target organ lesion and/or diabetes mellitus). Sitting blood pressure is taken after subjects take a seat to rest for 5 minutes before the next medication. Exclusion Criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Known or suspected secondary hypertension 2. Resting heart rate is < 55bpm. 3. Sick sinus syndrome 4. Atrioventricular block of first degree (with P-R>0. 24seconds), or second or third degree 5. Other clinical significant arrhythmia 6. Unstable and/or decompensated congestive heart failure 7. Angina, acute myocardial infarction, percutaneous coronary intervention (PCI), or cardiac surgery 8. Asthma or moderate to severe chronic obstructive pulmonary disease 9. Type 1 diabetes mellitus 10. Gout history 11. Fasting serum glucose of greater than 200 mg/dl (11. 1 mmol/L) or type 2 diabetes mellitus needs insulin therapy 12. ALT>3ULN 13. Cr>1. 5mg/dl 14. Pregnancy or lactation. 15. Alcohol or drug abuse 16. Known need for other concomitant anti-hypertensive therapy during the study besides the study drug. 17. Known or suspected allergy to investigational drug or non-active ingredients of investigational drugs, known allergy to other blockers, calcium antagonist, diuretics, angiotensin converting enzyme inhibitor or with other contraindications. 18. Suspected white-coat hypertension based on investigator's judgement.

CSR-D4385L00001.pdf

Starting date: December 2005
Last updated: March 13, 2015