The Effect of Losartan and Losartan Plus Isosorbide Mononitrate on Central Blood Pressure Measurements (0954-317)

• ClinicalTrials.gov Identifier: NCT00943852
• Recruitment Status: Completed
• First Posted: July 22, 2009
• Results First Posted: July 15, 2010
• Last Update Posted: February 9, 2022
• Sponsor: Organon and Co
• Information provided by (Responsible Party): Organon and Co

Study Description

Brief Summary:

This study will qualify a functional model that can measure central blood pressure and vascular compliance effects through noninvasive means.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: losartan potassium; Drug: Comparator: isosorbide mononitrate (ISMN); Drug: Comparator: losartan + ISMN; Drug: Comparator: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Diagnostic
• Official Title: A Double-Blind, Randomized, Placebo-Controlled, 5-Period Crossover Study to Evaluate the Effects of a Single Dose of Losartan, a Single Dose of Isosorbide Mononitrate (ISMN), and Single Doses of Losartan + ISMN on Central Blood Pressure Measurements in Mildly Hypertensive Patients
• Study Start Date: August 2006
• Actual Primary Completion Date: December 2006
• Actual Study Completion Date: December 2006

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1; losartan 100 mg	Drug: losartan potassium; Single dose losartan 100 mg in one of five treatment periods; Other Name: COZAAR
Active Comparator: 2; ISMN 60 mg	Drug: Comparator: isosorbide mononitrate (ISMN); Single dose ISMN 60 mg in one of five treatment periods; Other Name: IMDUR
Active Comparator: 3; losartan 100 mg + ISMN 15 mg	Drug: Comparator: losartan + ISMN; Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods
Active Comparator: 4; losartan 100 mg + ISMN 60 mg	Drug: Comparator: losartan + ISMN; Single dose losartan 100 mg and ISMN 60 mg in one of five treatment periods
Placebo Comparator: 5; Placebo	Drug: Comparator: Placebo; Single dose placebo only in one of five treatment periods

Outcome Measures

Primary Outcome Measures :

1. Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg Plus ISMN 60 mg Versus Single Dose of Losartan 100 mg [ Time Frame: Baseline and 10 hours postdose ]
   The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline.
2. Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo [ Time Frame: Baseline and 10 hours postdose ]

   The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P =

   pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patient is in good health with the exception of mild to moderate hypertension
• Patient is willing to comply with the study restrictions
• Patient does not smoke

Exclusion Criteria:

• Patient has a history of any illness that might confound the results of the study or make participation in the study unsafe
• Patient is taking a prescription medication that is contraindicated for use with COZAAR® or IMDUR®
• Patient has a condition for which there is a warning, contraindication, or precaution against the use of COZAAR® or IMDUR®

Contacts and Locations

Sponsors and Collaborators

Organon and Co

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Kaufman R, Nunes I, Bolognese JA, Miller DL, Salotti D, McCarthy JM, Smith WB, Herman GA, Feig PU. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens. 2010 Nov-Dec;4(6):311-8. doi: 10.1016/j.jash.2010.10.004.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00943852
• Other Study ID Numbers: 0954-317; MK0954-317; 2009_610
• First Posted: July 22, 2009
• Results First Posted: July 15, 2010
• Last Update Posted: February 9, 2022
• Last Verified: February 2022

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Losartan; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Diuretics, Osmotic; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Vasodilator Agents; Nitric Oxide Donors