The Effects of Systolic Blood Pressure Lowering on Diasto... | NCT00523549

NCT00523549

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Standard treatment regimen	Experimental	(Valsartan + Amlodipine to target SBP of < 140 mmHg)	Drug: valsartan Drug: amlodipine
Intensive treatment regimen	Experimental	(Valsartan + Amlodipine to target SBP < 130 mm Hg)	Drug: valsartan Drug: amlodipine

Name	Type	Description	Arm Group Labels	Other Names
valsartan	Drug	160 mg or 320 mg tablets once a day	Intensive treatment regimen Standard treatment regimen

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Lateral Mitral Annular Myocardial Relaxation Velocity	Change from baseline in lateral mitral annular myocardial relaxation velocity (E') at Week 24	Baseline to 24 weeks after treatment

Secondary Outcomes

Measure	Description	Time Frame
Change in Left Atrial Size	Change from baseline in left atrial size at Week 24	Baseline to 24 weeks after treatment
Change in Ratio of Peak E Wave Velocity/Lateral Mitral Annular Myocardial Relaxation Velocity

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 45 years or older
Male and female patients are eligible. Female patients must be post-menopausal for one year, surgically sterile, or using effective contraceptive methods such as a double barrier method with spermicide, an intra-uterine device, or hormonal contraceptives. Post-menopausal women on a stable dose of hormone replacement therapy (HRT) for at least three (3) months prior to the screening visit are eligible for the study.
Uncontrolled systolic hypertension on a maximum of two (2) antihypertensive medications at the time of screening.
Echocardiographic ejection fraction ≥50% and evidence of diastolic dysfunction.
Provide written informed consent to participate in the study prior to any screening or study procedures
Have the ability to communicate well and comply with all study requirements

Exclusion Criteria:

Severe hypertension defined as a MSSBP >200 mmHg and/or MSDBP >120 mmHg.
History of a secondary cause of hypertension including but not limited to: coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.
Ejection fraction <50 %
History of stroke, transient ischemic attack, myocardial infarction, coronary artery bypass graft surgery, or unstable angina pectoris within 6 months of screening
Presence of clinically significant ventricular or supraventricular arrhythmias (e.g. atrial fibrillation/flutter)
History of congestive heart failure
History of diabetes mellitus
History of renal impairment with serum creatinine >2.0 mg/dL at screening, history of dialysis, or history of nephritic syndrome
Antihypertensive therapy with three (3) or more medications at the time of screening
Active and/or treated malignancy of any organ system within twelve (12) months of enrollment, with the exception of localized basal cell carcinoma of the skin
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/ml)
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy OR are using one or more of the following acceptable methods of contraception: barrier method with spermicidal agent, an intrauterine device, hormonal contraceptives, or total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug including, but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active, or active inflammatory bowel syndrome within 12 months prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal bleeding, or urinary tract obstruction regarded as clinically meaningful by the investigator
Pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury within 12 months prior to Visit 1
Any serum AST or ALT elevation two (2) times the upper limit of normal

Other protocol-defined inclusion/exclusion criteria may apply

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Sites		USA	New Jersey		United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
19996069	Result	Solomon SD, Verma A, Desai A, Hassanein A, Izzo J, Oparil S, Lacourciere Y, Lee J, Seifu Y, Hilkert RJ, Rocha R, Pitt B; Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction Investigators. Effect of intensive versus standard blood pressure lowering on diastolic function in patients with uncontrolled hypertension and diastolic dysfunction. Hypertension. 2010 Feb;55(2):241-8. doi: 10.1161/HYPERTENSIONAHA.109.138529. Epub 2009 Dec 7.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Change from baseline in peak E-wave velocity / lateral mitral annular myocardial relaxation velocity (E/E') at Week 24

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
BG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000114 BG001114 BG002228

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Continuous

In this study, even though the number of patients randomized to the intensive and standard treatment regimen were 114 and 115 respectively, analysis of the Baseline Measures was performed using the Safety Population. The Safety Population included all randomized patients who received at least one dose of study medication (Number of patients= 114 in both the treatment arms).

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0001.544± 1.3946 OG0011.476± 1.5985

Secondary

Change in Left Atrial Size

Change from baseline in left atrial size at Week 24

Intent-to-treat

Posted

Mean

Standard Deviation

Baseline to 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Secondary

Change in Ratio of Peak E Wave Velocity/Lateral Mitral Annular Myocardial Relaxation Velocity

Change from baseline in peak E-wave velocity / lateral mitral annular myocardial relaxation velocity (E/E') at Week 24

Intent-to-treat

Posted

Mean

Standard Deviation

ratio

Baseline to 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Secondary

Percent Change From Baseline in Vascular Stiffness

Percent change from baseline in Vascular Stiffness (measured by radial augmentation index [AI]) at Weeks 8 and 24

Intent-to-treat

Posted

Mean

Standard Deviation

percentage of change in mean AI

Baseline to 8 and 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Secondary

Change in Mean Sitting Systolic Blood Pressure (msSBP)

Change from baseline in msSBP at Weeks 8 and 24

Intent-to-treat

Posted

Mean

Standard Deviation

mm Hg

Baseline to 8 and 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Secondary

Change in Mean Sitting Diastolic Blood Pressure (msDBP)

Change from baseline in msDBP at Weeks 8 and 24

Intent-to-treat population

Posted

Mean

Standard Deviation

mm Hg

Baseline to 8 and 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Secondary

Change in Estimated Central Aortic Pressure

Change from baseline in estimated central aortic pressure at Weeks 8 and 24

Intent-to-treat

Posted

Mean

Standard Deviation

mm Hg

Baseline to 8 and 24 weeks after treatment

ID	Title	Description
OG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.
OG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intensive Treatment Regimen	(Valsartan + Amlodipine to target SBP < 130 mm Hg). Patients in the intensive treatment regimen had the study medication force-titrated to the maximum tolerated dose with the goal to achieve an SBP < 130 mm Hg. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2, patients were force-titrated to valsartan 160 mg + amlodipine 10 mg. At week 4, patients were force titrated to valsartan 320 mg + amlodipine 10 mg. At week 8, patients who reached the SBP target < 130 mm Hg stayed on their current dose valsartan 320 mg + amlodipine 10 mg or the maximum tolerated dose as per the investigator's discretion. Patients not at SBP target < 130 mm Hg at week 8 or any study visits thereafter received other additional antihypertensive medications.			3	114	49	114
EG001	Standard Treatment Regimen	(Valsartan + Amlodipine to target SBP of < 140 mmHg). Patients in the standard treatment regimen had the study medication up-titrated until the SBP goal of < 140 mm Hg was achieved. At week 0 patients received valsartan 160 mg + amlodipine 5 mg. At week 2 patients were up-titrated to valsartan 160 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. At week 4 patients were up-titrated to valsartan 320 mg + amlodipine 10 mg only if they were not at SBP target < 140 mm Hg. Patients not at SBP target < 140 mm Hg by Week 8 or at any study visit thereafter received additional antihypertensive medications.			3	114	41	114

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected114 at risk EG0010 affected114 at risk
Goitre	Endocrine disorders	MedDRA	Systematic Assessment	EG0001 affected114 at risk EG0010 affected114 at risk
Appendicitis perforated	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Abdominal abscess	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Pneumonia	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected114 at risk EG0011 affected114 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected114 at risk EG0010 affected114 at risk
Thyroid adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected114 at risk EG0010 affected114 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected114 at risk EG0010 affected114 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA	Systematic Assessment	EG00012 affected114 at risk EG0017 affected114 at risk
Oedema peripheral	General disorders	MedDRA	Systematic Assessment	EG00024 affected114 at risk EG00120 affected114 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0008 affected114 at risk EG0017 affected114 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0006 affected114 at risk EG0014 affected114 at risk
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG00016 affected114 at risk EG0019 affected114 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected114 at risk EG0018 affected114 at risk

Title	Organization	Phone	Extension	Email
Study Director	Novartis Pharmaceuticals	862-778-8300

ID	Term
D006973	Hypertension

ID	Term
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Term
D000068756	Valsartan
D017311	Amlodipine

Ancestor Terms

ID	Term
D013777	Tetrazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014633	Valine
D000597	Amino Acids, Branched-Chain
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000601	Amino Acids, Essential
D004095	Dihydropyridines
D011725	Pyridines