Trial Outcomes & Findings for A 52 Week Study to Evaluate the Effects of Losartan With or Without HCTZ on Plasma Glucose, Metabolic Parameters, Blood Pressure in Hypertensive Patients With Metabolic Syndrome (0954A-331) (NCT NCT00546052)

NCT ID: NCT00546052

Last Updated: 2024-05-16

Results Overview

Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1738 participants
• Primary outcome timeframe: 52 Weeks - Baseline
• Results posted on: 2024-05-16

Participant Flow

First Patient In: 12-Sep-2005 Last Patient In: 29-Dec-2006 Last Patient Last Visit: 31-Jan-08 Total number of Sites (General Practitioners and Family Physicians in Canada): 209

24 patients not included in the Intention to Treat (ITT) analysis because they did not receive study medication and had no follow up visits. Total ITT population = 1714.

Participant milestones

Measure	Losartan +/- Hydrochlorothiazide Patients could be titrated up from Cozaar 50 mg to Cozaar 100mg to losartan 100 mg + Hydrochlorothiazide 12.5 mg and losartan 100mg/ Hydrochlorothiazide 25 mg, in sequence at any subsequent visits only if needed to obtain Blood Pressure under 140/90 mm Hg.
Overall Study STARTED	1738
Overall Study Week 4	1714
Overall Study Week 8	1680
Overall Study Week 12	1650
Overall Study Week 32	1583
Overall Study Week 52	1511
Overall Study COMPLETED	1511
Overall Study NOT COMPLETED	227

Reasons for withdrawal

Measure	Losartan +/- Hydrochlorothiazide Patients could be titrated up from Cozaar 50 mg to Cozaar 100mg to losartan 100 mg + Hydrochlorothiazide 12.5 mg and losartan 100mg/ Hydrochlorothiazide 25 mg, in sequence at any subsequent visits only if needed to obtain Blood Pressure under 140/90 mm Hg.
Overall Study Adverse Event	47
Overall Study Lost to Follow-up	144
Overall Study Protocol Violation	9
Overall Study Withdrawal by Subject	20
Overall Study Non Compliance	7

Baseline Characteristics

A 52 Week Study to Evaluate the Effects of Losartan With or Without HCTZ on Plasma Glucose, Metabolic Parameters, Blood Pressure in Hypertensive Patients With Metabolic Syndrome (0954A-331)

Baseline characteristics by cohort

Measure	Losartan +/- Hydrochlorothiazide n=1714 Participants Patients could be titrated up from Cozaar 50 mg to Cozaar 100mg to losartan 100 mg + Hydrochlorothiazide 12.5 mg and losartan 100mg/ Hydrochlorothiazide 25 mg, in sequence at any subsequent visits only if needed to obtain Blood Pressure under 140/90 mm Hg.
Age, Continuous	54.93 Years STANDARD_DEVIATION 11.29 • n=93 Participants
Age, Customized <=45.00	326 participants n=93 Participants
Age, Customized 45.01 - 52.00	359 participants n=93 Participants
Age, Customized 52.01 - 58.00	356 participants n=93 Participants
Age, Customized 58.01 - 65.00	346 participants n=93 Participants
Age, Customized >=65.00	326 participants n=93 Participants
Age, Customized Missing	1 participants n=93 Participants
Sex: Female, Male Female	734 Participants n=93 Participants
Sex: Female, Male Male	980 Participants n=93 Participants
Race/Ethnicity, Customized Caucasian	1451 participants n=93 Participants
Race/Ethnicity, Customized Black	32 participants n=93 Participants
Race/Ethnicity, Customized Asian	200 participants n=93 Participants
Race/Ethnicity, Customized Native American	11 participants n=93 Participants
Race/Ethnicity, Customized Other	19 participants n=93 Participants
Race/Ethnicity, Customized Missing	1 participants n=93 Participants
Body Mass Index	33.23 Kg/m2 STANDARD_DEVIATION 5.59 • n=93 Participants
C-Reactive Protein	5.4 mg/L STANDARD_DEVIATION 8.8 • n=93 Participants
Diastolic Blood Pressure	90.54 mm Hg STANDARD_DEVIATION 8.16 • n=93 Participants
Fasting Blood Glucose	5.7 mmol/L STANDARD_DEVIATION 0.7 • n=93 Participants
Heart Rate	75 Beats per Minute (BPM) STANDARD_DEVIATION 8.0 • n=93 Participants
Hemoglobin A1c	5.71 Percent STANDARD_DEVIATION 0.59 • n=93 Participants
High Density Lipoprotein-C	1.23 mol/L STANDARD_DEVIATION 0.33 • n=93 Participants
Low Density Lipoprotein-C	3.17 mmol/L STANDARD_DEVIATION 0.93 • n=93 Participants
Systolic Blood Pressure	148.22 mm Hg STANDARD_DEVIATION 10.72 • n=93 Participants
Total Cholesterol	5.36 mmol/L STANDARD_DEVIATION 1.05 • n=93 Participants
Triglycerides	2.16 mmol/L STANDARD_DEVIATION 1.16 • n=93 Participants
Uric Acid	365.8 mmol/L STANDARD_DEVIATION 85.4 • n=93 Participants
Weight	92.5 Kilograms (Kg) STANDARD_DEVIATION 18.1 • n=93 Participants

PRIMARY outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute Change in Hemoglobin A1c between 52 week measurement and baseline value.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Hemoglobin A1c Between 52 Weeks and Baseline	0.04 Percent Standard Deviation 0.62	—	—

PRIMARY outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute Change in Fasting Blood Glucose Measurements between Baseline and 52 week assessments.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Fasting Blood Glucose Between Baseline and 52 Weeks Assessments	0.02 mmol/L Standard Deviation 0.74	—	—

SECONDARY outcome

Timeframe: 52 Weeks

Population: ITT and Per Protocol

Target Blood Pressure defined as Systolic Blood Pressure/Diastolic Blood Pressure ≤ 140/90 mm Hg at 52 weeks

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1738 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat n=1714 Participants All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol n=1511 Participants All patients completing the 52 week study follow up.
Target Blood Pressure Achieved Target Blood Pressure	1200 Participants	1200 Participants	1200 Participants
Target Blood Pressure Did NOT achieve target Blood Pressure	538 Participants	514 Participants	311 Participants

SECONDARY outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute change in Systolic Blood Pressure between baseline and 52 week assessments.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Systolic Blood Pressure Between Baseline and 52 Week Assessments	-16.95 mm Hg Standard Deviation 13.34	—	—

SECONDARY outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute change in Diastolic Blood Pressure between baseline and 52 week assessments.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Diastolic Blood Pressure Between Baseline and 52 Week Assessments	-9.84 mm Hg Standard Deviation 8.93	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute change in Waist Circumference between baseline and 52 week assessments

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Waist Circumference Between Baseline and 52 Week Assessments	-1.28 cm Standard Deviation 5.44	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute change in Body Mass Index Baseline and 52 week assessments

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Change in Body Mass Index Between Baseline and 52 Week Assessments	-7.3 Kg/m2 Standard Deviation 5.20	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Percent Change in LDL-C Between Baseline and 52 week assessments: 100% x [(LDL-C 52 Weeks - LDL-C Baseline) / (LDL-C Baseline)].

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Percent Change in Low Density Lipoprotein-C Between Baseline and 52 Week Assessments	-1.49 Percent Change Standard Deviation 32.10	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Percent Change in HDL-C Between Baseline and 52 week assessments: 100% x [(HDL-C 52 Weeks - HDL-C 52 Baseline) / (HDL-C Baseline)].

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Percent Change in High Density Lipoprotein-C Between Baseline and 52 Week Assessments	0.21 Percent Change Standard Deviation 17.96	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Percent Change in Triglycerides Between Baseline and 52 week assessments: 100% x [(Triglycerides 52 Weeks - Triglycerides Baseline) / (Triglycerides Baseline)].

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Percent Change in Triglycerides Between Baseline and 52 Week Assessments	1.09 Percent Change Standard Deviation 43.54	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Percent Change in Total Cholesterol Between Baseline and 52 week assessments: 100% x [(Total Cholesterol 52 weeks - Total Cholesterol Baseline) / (Total Cholesterol Baseline)].

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Percent Change in Total Cholesterol Between Baseline and 52 Week Assessments	-2.98 Percent Change Standard Deviation 16.97	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute Change in Uric Acid Between Baseline and 52 week assessments: Uric Acid 52 weeks - Uric Acid Baseline.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Absolute Change in Uric Acid Between Baseline and 52 Week Assessments	-19.17 mmol/L Standard Deviation 63.84	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 Weeks - Baseline

Population: Per Protocol

Absolute Change in C Reactive Protein Between Baseline and 52 week assessments: C Reactive Protein 52 weeks - C Reactive Protein Baseline.

Outcome measures

Measure	Losartan +/- Hydrochlorothiazide n=1511 Participants Patients that completed 52 weeks of treatment and were \>= 80% compliant with the study medication.	Overall Intend to Treat All patients enrolled and receiving at least one dose of study drug and having at least one follow up visit.	Overall Per Protocol All patients completing the 52 week study follow up.
Absolute Change in C Reactive Protein Between Baseline and 52 Week Assessments	-0.36 mg/L Standard Deviation 8.66	—	—

Adverse Events

Overall ITT

Serious events: 35 serious events

Other events: 198 other events

Deaths: 0 deaths

Serious adverse events

Measure	Overall ITT n=1714 participants at risk
Cardiac disorders Acute coronary syndrome	0.06% 1/1714
Psychiatric disorders Acute depression	0.06% 1/1714
Renal and urinary disorders Acute renal insufficiency	0.06% 1/1714
Immune system disorders Anaphylactic shock	0.06% 1/1714
Immune system disorders Anaphylaxis	0.06% 1/1714
Injury, poisoning and procedural complications Ankle fracture	0.06% 1/1714
Vascular disorders Atherosclerotic cardiovascular disease	0.06% 1/1714
Cardiac disorders Atrial flutter	0.06% 1/1714
Respiratory, thoracic and mediastinal disorders Bronchitis asthmatic	0.06% 1/1714
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer	0.18% 3/1714
Surgical and medical procedures Cardiac catheterization	0.06% 1/1714
Cardiac disorders Cardiomyopathy	0.06% 1/1714
Nervous system disorders Cerebral vascular accident	0.18% 3/1714
General disorders Chest Pain	0.06% 1/1714
General disorders Death	0.12% 2/1714
Gastrointestinal disorders Gastric Ulcer	0.06% 1/1714
Surgical and medical procedures Hip Replacement	0.12% 2/1714
Surgical and medical procedures Ileostomy	0.06% 1/1714
Cardiac disorders Infarction	0.06% 1/1714
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma grade IV	0.06% 1/1714
Nervous system disorders Multiple sclerosis aggravated	0.06% 1/1714
Gastrointestinal disorders Nausea	0.06% 1/1714
Gastrointestinal disorders Vomiting	0.06% 1/1714
Nervous system disorders Numbness of Upper Arm	0.06% 1/1714
Infections and infestations Pneumonia	0.06% 1/1714
Surgical and medical procedures Rotator Cuff Repair	0.06% 1/1714
Cardiac disorders Single Vessel Disease	0.06% 1/1714
Nervous system disorders Subarachnoid Hemorrhage	0.06% 1/1714
Vascular disorders Superficial Femoral Arterial Stenosis	0.06% 1/1714
Gastrointestinal disorders Ulcer Bleeding Gastric	0.06% 1/1714

Other adverse events

Measure	Overall ITT n=1714 participants at risk
Metabolism and nutrition disorders Type 2 diabetes mellitus	3.2% 54/1714
Nervous system disorders Dizziness	2.0% 35/1714
Respiratory, thoracic and mediastinal disorders Bronchitis	1.7% 29/1714
Musculoskeletal and connective tissue disorders Osteoarthritis	1.3% 23/1714
Nervous system disorders Headache	1.2% 21/1714
Infections and infestations Sinusitis	1.1% 19/1714
Investigations Blood Glucose Increased (per investigator's clinical judgment)	0.99% 17/1714

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER