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

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Felodipine tablet (Plendil) alone; Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK); Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril); Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide

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 Type: Interventional
• Enrollment (Actual): 529
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Felodipine tablet (Plendil)	Drug: Felodipine tablet (Plendil) alone; Felodipine sustained release tablet single drug therapy (1st week- 2nd week) Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is controlled after 2 weeks, then the subjects will continue the treatment until the end of primary therapy stage (14th week).
Active Comparator: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK)	Drug: Felodipine tablet (Plendil)+Metoprolol tablet (Betaloc ZOK); Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with metoprolol succinate prolonged-release tablet (Betaloc ZOK) 47.5mg , once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.
Active Comparator: Felodipine tablets (Plendil)+Lisinopril (Zestril)	Drug: Felodipine tablets (Plendil)+Lisinopril (Zestril); Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with Lisinopril (Zestril) 10mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.
Active Comparator: Felodipine tablet (Plendil)+Hydrochlorothiazide	Drug: Felodipine tablet (Plendil)+Hydrochlorothiazide; Step 1: Eligible subjects will first take felodipine tablet 5mg, once daily, orally for 2 weeks. If blood pressure is not controlled after 2 weeks, then the subjects will go to Step 2: Felodipine sustained release tablet 5mg once daily combined with hydrochlorothiazide 12.5mg, once daily. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 3: The dosage of felodipine sustained release tablet will be escalated to 10mg, once daily, while the dosage of the combined drug remains the same. If blood pressure is not controlled after 4 weeks, then the subjects will go to Step 4: The dosage of felodipine sustained release tablet keeps 10mg, once daily, while the dosage of different combined drug is doubled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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 duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.	4 weeks
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 duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.	8 weeks
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 duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.	4 weeks
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 duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.	8 weeks
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 duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial.	12 weeks
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 duration of the combination therapy was 4 weeks. Blood pressure was measured at week 6 of the trial.	4 weeks
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 duration of the combination therapy was 8 weeks. Blood pressure was measured at week 10 of the trial.	8 weeks
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 duration of the combination therapy was 12 weeks. Blood pressure was measured at week 14 of the trial.	12 weeks
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 duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial.	12 weeks
The Change of Pulse Wave Velocity From Baseline at 2, 14 Weeks of Felodipine Sustained Release Alone.	The duration of the combination therapy was 12 weeks. The change of pulse wave velocity was measured at week 14 of the trial.	12 weeks
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	The duration of the combination therapy was 2 weeks. Blood pressure was measured at week 2 of the trial.	2 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Ningling Sun, PhD, MD, Beijing University People's Hospital, Department of Cardiology

Publications and helpful links

Helpful Links

• Related Info
• CSR-D4385L00001.pdf

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: November 25, 2014
• First Submitted That Met QC Criteria: January 8, 2015
• First Posted (Estimate): January 13, 2015

Study Record Updates

• Last Update Posted (Estimate): March 23, 2015
• Last Update Submitted That Met QC Criteria: March 13, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Protease Inhibitors; Protective Agents; Natriuretic Agents; Cardiotonic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin-Converting Enzyme Inhibitors; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide; Metoprolol; Felodipine; Lisinopril
• Other Study ID Numbers: D4385L00001