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

Not Applicable

Completed

• Conditions: Hypertension
• Interventions: Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide; Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril); Drug: Felodipine tablet (Plendil) alone; Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)

• Registration Number: NCT02336607
• Lead Sponsor: AstraZeneca

Brief Summary

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.

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.

Study Timeline

• Study Start: 2005-12
• Primary Completion: 2006-06
• Study Completion: 2006-08
• Study First Submitted: 2014-11-25
• Study First Submitted QC: 2015-01-08
• Results First Submitted: 2015-01-12
• Study First Posted: 2015-01-13
• Status Verified: 2015-03
• Results First Submitted QC: 2015-03-13
• Last Update Submitted: 2015-03-13
• Results First Posted: 2015-03-23
• Last Update Posted: 2015-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 529

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Felodipine tablet (Plendil)+Hydrochlorothiazide	Felodipine tablet (Plendil)+Hydrochlorothiazide	-
Felodipine tablets (Plendil)+Lisinopril (Zestril)	Felodipine tablets (Plendil)+Lisinopril (Zestril)	-
Felodipine tablet (Plendil)	Felodipine tablet (Plendil) alone	-
Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)	Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)	-

Primary Outcome Measures

Name	Time	Method
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.	14 weeks

Secondary Outcome Measures

Name	Time	Method
The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone.	12 weeks	The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial.
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	2 weeks	The duration of the combination therapy was 2 weeks. Blood pressure was measured at week 2 of the trial.
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.	8 weeks	The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.
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.	4 weeks	The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.
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.	4 weeks	The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.
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.	8 weeks	The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.
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.	12 weeks	The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial.
The Change of Pulse Wave Velocity at 12 Weeks Compare With Baseline Data of Felodipine Sustained Release in Combination With Metoprolol, Lisinopril or Hydrochlorothiazide.	12 weeks	The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial.
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.	4 weeks	The duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.
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.	8 weeks	The duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.
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.	12 weeks	The duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial.