Trial Outcomes & Findings for Obese Hypertension Study (0954-315) (NCT NCT00289887)

NCT ID: NCT00289887

Last Updated: 2022-02-09

Results Overview

Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 8. A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment\*week, and week\*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 261 participants
• Primary outcome timeframe: At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)
• Results posted on: 2022-02-09

Participant Flow

Patients were recruited at 51 sites in the United States. Prime Therapy Period: April 2006 to February 2007

Prior antihypertensive medications were withdrawn/ tapered before patients entered the 4-week placebo run-in period.

Participant milestones

Measure	Losartan Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Overall Study STARTED	127	134
Overall Study COMPLETED	105	105
Overall Study NOT COMPLETED	22	29

Reasons for withdrawal

Measure	Losartan Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Overall Study Adverse Event	3	3
Overall Study Lack of Efficacy	3	11
Overall Study Lost to Follow-up	3	3
Overall Study Protocol Violation	3	1
Overall Study Withdrawal by Subject	3	8
Overall Study Other	7	3

Baseline Characteristics

Obese Hypertension Study (0954-315)

Baseline characteristics by cohort

Measure	Losartan n=127 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=134 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg	Total n=261 Participants Total of all reporting groups
Age, Continuous	50.1 years STANDARD_DEVIATION 10.4 • n=5 Participants	51.4 years STANDARD_DEVIATION 9.7 • n=7 Participants	50.8 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	77 Participants n=7 Participants	156 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	57 Participants n=7 Participants	105 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	84 participants n=5 Participants	87 participants n=7 Participants	171 participants n=5 Participants
Race/Ethnicity, Customized Black	22 participants n=5 Participants	29 participants n=7 Participants	51 participants n=5 Participants
Race/Ethnicity, Customized Hispanic American	20 participants n=5 Participants	16 participants n=7 Participants	36 participants n=5 Participants
Race/Ethnicity, Customized Native American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Sitting Diastolic Blood Pressure (SiDBP)	99.1 mm Hg STANDARD_DEVIATION 4.2 • n=5 Participants	99.0 mm Hg STANDARD_DEVIATION 4.0 • n=7 Participants	99.0 mm Hg STANDARD_DEVIATION 4.1 • n=5 Participants
Sitting Systolic Blood Pressure (SiSBP)	151.6 mm Hg STANDARD_DEVIATION 8.2 • n=5 Participants	152.4 mm Hg STANDARD_DEVIATION 9.0 • n=7 Participants	152.0 mm Hg STANDARD_DEVIATION 8.6 • n=5 Participants

PRIMARY outcome

Timeframe: At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 8.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=119 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=117 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 8	-12.1 mm Hg Standard Error 1.2	-6.8 mm Hg Standard Error 1.2

PRIMARY outcome

Timeframe: At baseline and at 8 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 8.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=119 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=117 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 8	-9.7 mm Hg Standard Error 0.8	-6.9 mm Hg Standard Error 0.8

PRIMARY outcome

Timeframe: At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 12.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=109 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=112 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 12	-12.9 mm Hg Standard Error 0.8	-7.1 mm Hg Standard Error 0.8

PRIMARY outcome

Timeframe: At baseline and at 12 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 12.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=109 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=112 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 12	-16.7 mm Hg Standard Error 1.3	-6.8 mm Hg Standard Error 1.3

PRIMARY outcome

Timeframe: At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after last morning dose) SiSBP at Week 16.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=106 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=106 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Systolic Blood Pressure (SiSBP) at Week 16	-19.1 mm Hg Standard Error 1.3	-6.4 mm Hg Standard Error 1.3

PRIMARY outcome

Timeframe: At baseline and at 16 weeks (with the measurements taken prior to the morning dose, between 6 AM and 10 AM)

Population: An "all patients treated" approach was employed, patients included had at least 1 dose post baseline and 1 measurement at baseline and during treatment.

Mean change from baseline in trough (6 hours after the last morning dose) SiDBP at Week 16.

A mixed effects model (with repeated measurements including terms of treatment, investigators, week, baseline SiSBP(/SiDBP), plasma glucose stratum, treatment*week, and week*SiSBP(/SiDBP)) was used to compare the treatments on the change from baseline.

Outcome measures

Measure	Losartan n=106 Participants Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=106 Participants Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Mean Change From Baseline in Trough Sitting Diastolic Blood Pressure (SiDBP) at Week 16	-14.1 mm Hg Standard Error 0.9	-6.0 mm Hg Standard Error 0.9

Adverse Events

Losartan

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Losartan n=127 participants at risk Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=134 participants at risk Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Gastrointestinal disorders Pancreatitis acute	0.79% 1/127 • Week 0 through Week 16.	0.00% 0/134 • Week 0 through Week 16.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/127 • Week 0 through Week 16.	0.75% 1/134 • Week 0 through Week 16.

Other adverse events

Measure	Losartan n=127 participants at risk Once-daily losartan 50 mg titrated at 4-week intervals to losartan 100 mg, losartan 100 mg/Hydrochlorothiazide (HCTZ) 12.5 mg, and losartan 100 mg/HCTZ 25 mg	Placebo n=134 participants at risk Once-daily matching placebo for losartan 50 mg titrated at 4-week intervals to matching placebo for losartan 100 mg, matching placebo for losartan 100 mg/HCTZ 12.5 mg, and matching placebo for losartan 100 mg/HCTZ 25 mg
Nervous system disorders Headache	3.1% 4/127 • Week 0 through Week 16.	5.2% 7/134 • Week 0 through Week 16.

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