Trial Outcomes & Findings for LAAS (Losartan Anti-Atherosclerosis Study)(0954-330)(COMPLETED) (NCT NCT00496834)

NCT ID: NCT00496834

Last Updated: 2024-05-22

Results Overview

Analysis was performed in the modified intention to treat (mITT) population.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

201 participants

Primary outcome timeframe

Baseline and 24 Weeks

Results posted on

2024-05-22

Participant Flow

7 centers participated in this study (7 medical centers of university). FPE (First patient enrolled): Feb-2008, FPI (First patient in): Feb-2008, LPO (Last patient out): Sep-2009

Participant milestones

Participant milestones
Measure	Losartan Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Carvedilol Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).
Overall Study STARTED	101	100
Overall Study COMPLETED	83	87
Overall Study NOT COMPLETED	18	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Losartan Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Carvedilol Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).
Overall Study Withdrawal by Subject	4	6
Overall Study Contraindicated medication administered	0	1
Overall Study Inclusion/exclusion criteria not met	3	2
Overall Study Adverse Event	5	3
Overall Study IP administration violation	2	0
Overall Study Lost to Follow-up	2	0
Overall Study Blood Pressure control failure	2	1

Baseline Characteristics

LAAS (Losartan Anti-Atherosclerosis Study)(0954-330)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Losartan n=101 Participants Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Carvedilol n=100 Participants Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan).	Total n=201 Participants Total of all reporting groups
Age, Continuous	49.0 years STANDARD_DEVIATION 9.3 • n=5 Participants	50.1 years STANDARD_DEVIATION 10.2 • n=7 Participants	49.6 years STANDARD_DEVIATION 9.7 • n=5 Participants
Age, Customized >= 18 to < 65 years	96 participants n=5 Participants	91 participants n=7 Participants	187 participants n=5 Participants
Age, Customized >=65 years	5 participants n=5 Participants	9 participants n=7 Participants	14 participants n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	57 Participants n=7 Participants	120 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	43 Participants n=7 Participants	81 Participants n=5 Participants
DBP (diastolic blood pressure)	96.4 mm Hg STANDARD_DEVIATION 8.8 • n=5 Participants	96.4 mm Hg STANDARD_DEVIATION 8.3 • n=7 Participants	96.4 mm Hg STANDARD_DEVIATION 8.5 • n=5 Participants
Height	164.9 Centimeters STANDARD_DEVIATION 7.8 • n=5 Participants	163.3 Centimeters STANDARD_DEVIATION 9.2 • n=7 Participants	164.1 Centimeters STANDARD_DEVIATION 8.5 • n=5 Participants
PWV (pulse wave velocity)	7.6 meters/second STANDARD_DEVIATION 1.4 • n=5 Participants	7.7 meters/second STANDARD_DEVIATION 1.4 • n=7 Participants	7.6 meters/second STANDARD_DEVIATION 1.4 • n=5 Participants
Pulse	71.8 BPM (beats per minute) STANDARD_DEVIATION 10.0 • n=5 Participants	72.3 BPM (beats per minute) STANDARD_DEVIATION 10.0 • n=7 Participants	72.0 BPM (beats per minute) STANDARD_DEVIATION 10.0 • n=5 Participants
SBP (systolic blood pressure)	150.6 mm Hg STANDARD_DEVIATION 11.0 • n=5 Participants	152.7 mm Hg STANDARD_DEVIATION 12.1 • n=7 Participants	151.6 mm Hg STANDARD_DEVIATION 11.6 • n=5 Participants
Weight	70.9 Kilograms STANDARD_DEVIATION 10.6 • n=5 Participants	69.9 Kilograms STANDARD_DEVIATION 13.2 • n=7 Participants	70.4 Kilograms STANDARD_DEVIATION 12.0 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Population: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94). Missing data were imputed by the last observation carried forward (LOCF) technique.

Analysis was performed in the modified intention to treat (mITT) population.

Outcome measures

Outcome measures
Measure	Losartan n=88 Participants Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Carvedilol n=94 Participants Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Pulse Wave Velocity (PWV) Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug	0.28 meters/second Standard Deviation 1.29	-0.12 meters/second Standard Deviation 1.55

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Population: Participants for analysis was per protocol (Number of patients: Losartan group was 54, Carvedilol group was 67). Missing data were imputed by the last observation carried forward (LOCF) technique. For the primary efficacy endpoints, Per protocol analysis approach was supplementary used.

Analysis was performed in the per protocol (PP) population which additionally excludes certain protocol violations as described in the analysis plan.

Outcome measures

Outcome measures
Measure	Losartan n=54 Participants Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Carvedilol n=67 Participants Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
PWV Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug	0.16 meters/second Standard Deviation 1.25	-0.20 meters/second Standard Deviation 1.50

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Participants for analysis was modified intention to treat (Number of patients: Losartan group was 88, Carvedilol group was 94) Missing data were imputed by the last observation carried forward (LOCF) technique.

Outcome measures

Outcome measures
Measure	Losartan n=88 Participants Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Carvedilol n=94 Participants Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Systolic Blood Pressure (SBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug	-15.08 mm Hg Standard Deviation 14.59	-14.81 mm Hg Standard Deviation 15.38

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Outcome measures

Outcome measures
Measure	Losartan n=88 Participants Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.	Carvedilol n=94 Participants Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Patients who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who 1) had baseline measurements before randomization, 2) had taken the study drug more than once after randomization, 3) had one measurement after the initiation of the administration and 4) did not commit major violation.
Diastolic Blood Pressure (DBP) Mean Changes From Baseline (Visit 2) to 24 Weeks (Visit 6) After the Administration of the Study Drug	-8.43 mm Hg Standard Deviation 9.29	-7.81 mm Hg Standard Deviation 9.61

Adverse Events

Losartan

Serious events: 5 serious events

Other events: 35 other events

Deaths: 0 deaths

Carvedilol

Serious events: 6 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Losartan n=101 participants at risk Once daily , Cozaar® (losartan) 50 mg, Cozaar® (losartan) 100 mg, Cozaar Plus®-pro Tab. (losartan 100 mg / hydrochrolorothiazide 12.5 mg) or Cozaar Plus®-F Tab. (losartan 100 mg / hydrochrolorothiazide 25 mg), 24 weeks (Subjects who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who received the investigational drug at least more than once.	Carvedilol n=100 participants at risk Once daily, Dilatrend Tab® (carvedilol) 12.5 mg, Dilatrend Tab® (carvedilol) 25 mg, Dilatrend Tab® (carvedilol) 25 mg plus half Dichlozid Tab® (hydrochlorothiazide 25 mg) or Dilatrend Tab® (carvedilol) 25 mg plus full Dichlozid Tab® (hydrochlorothiazide 25 mg), 24 weeks (Subjects who have failed in blood pressure control, increase the study medication dose step by step according to the titration plan) and patients who received the investigational drug at least more than once.
Nervous system disorders Myelitis transverse	0.00% 0/101 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	1.0% 1/100 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Gastrointestinal disorders Mouth haemorrhage	0.99% 1/101 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	0.00% 0/100 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Infections and infestations Chronic sinusitis	0.00% 0/101 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	1.0% 1/100 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Injury, poisoning and procedural complications Overdose	0.99% 1/101 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	5.0% 5/100 • Number of events 5 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Injury, poisoning and procedural complications Ligament sprain	0.99% 1/101 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	0.00% 0/100 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Cardiac disorders Prinzmetal angina	0.99% 1/101 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	0.00% 0/100 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.
Vascular disorders Haematoma	0.99% 1/101 • Number of events 1 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.	0.00% 0/100 • Adverse events were recorded from first administration of study drug up to 14 days after the administration of final dose.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

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