Efficacy of Losartan + Amlodipine Compared to Amlodipine Alone in the Treatment of Uncontrolled High Blood Pressure (MK-0954F-399)

The 8 Weeks, Multicenter, Randomized, Double-blind, Clinical Study To Evaluate Efficacy Of Treatment With Losartan/Amlodipine 100/5 mg Combination Compared To Amlodipine 10 mg Monotherapy In Hypertensive Patients Who Are Not Appropriately Respond To Amlodipine 5 mg Monotherapy

This study will determine whether using losartan and amlodipine together will be non-inferior in lowering blood pressure than amlodipine alone.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Losartan (+) amlodipine; Drug: Placebo to match amlodipine; Drug: Placebo to match losartan/amlodipine tablets; Drug: Amlodipine camsylate

• Study Type: Interventional
• Enrollment (Actual): 334
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

• Participants with essential hypertension:

  • who are on single drug therapy
  • who are newly diagnosed and not yet taking any drug therapy, or have not had any drug therapy for at least 2 weeks prior to entering study
  • who have blood pressure readings of 90mmHg ≤ MSDBP < 110mmHg and 140mmHg ≤ MSSBP <180mmHg after 2 weeks wash-out for patients on single agent.

• Randomization (Visit 3)

  • After dosing of amlodipine 5mg for 6 weeks, blood pressure readings are:

    • 90mmHg ≤ MSDBP < 110mmHg and 140mmHg ≤ MSSBP < 180mmHg.

Exclusion criteria

• Participant with MSDBP ≥ 110mmHg or MSSBP ≥ 180mmHg.
• Participant currently taking ≥ 2 antihypertensive medications (note: fixed-dose combination medicine should be counted as the number of active ingredients).
• Participant with known secondary hypertension of any etiology.
• Participant with malignant hypertension or current evidence of impending or active malignant hypertension, including headache, papilledema, cardiac ischemia, or pulmonary congestion precipitated by elevated blood pressure.
• Participant with known intolerance, contraindication or hypersensitivity to any component of dihydropyridines, angiotensin II receptor blockers.
• Participant showing positive in pregnancy test, lactating woman, or woman who intends to get pregnant during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan/amlodipine Treatment Arm; One combination tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks. Participants will also receive 2 tablets of placebo for amlodipine 5mg orally, once daily for 8 weeks.	Drug: Losartan (+) amlodipine; One tablet containing 100 mg losartan potassium and 5 mg amlodipine camsylate, orally, once daily, for 8 weeks.; Other Names: COZAAR XQ™; Drug: Placebo to match amlodipine; 2 tablets containing placebo, orally, once daily, for 8 weeks.
Active Comparator: Amlodipine Treatment Arm; 2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks. Participants will also receive 1 tablet of placebo for combination losartan/amlodipine orally, once daily for 8 weeks.	Drug: Placebo to match losartan/amlodipine tablets; One tablet containing placebo, orally, once daily, for 8 weeks.; Drug: Amlodipine camsylate; 2 tablets each containing 5 mg amlodipine, orally, once daily, for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 8	Diastolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.	Baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) at Week 4	Diastolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.	Baseline and Week 4
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 8	Systolic blood pressure was assessed at baseline and after 8 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.	Baseline and Week 8
Change in Mean Sitting Systolic Blood Pressure (MSSBP) at Week 4	Systolic blood pressure was assessed at baseline and after 4 weeks of treatment with the participant in a seated position using an auto sphygmomanometer. Three measurements were performed at 2-minute intervals and the average of the 3 values of was recorded.	Baseline and Week 4
Percentage of Participants Who Achieve Target Blood Pressure at Week 8	Participants were evaluated at Week 8 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) <90mmHg or sitting systolic BP (sitSBP) <140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.	Week 8
Percentage of Participants Who Achieve Target Blood Pressure at Week 4	Participants were evaluated at Week 4 to ascertain if target blood pressure had been obtained. Criteria for meeting target BP were: sitting diastolic BP (sitDBP) <90mmHg or sitting systolic BP (sitSBP) <140mmHg) or sitDBP change more than 10mmHg from baseline or sitSBP change more than 20mmHg from baseline.	Week 4
Percentage of Participants Who Had Peripheral Edema During the Study	A pitting assessment of edema on both legs was performed at baseline and throughout the study. Participants were assessed in a seated position with both feet extended and the right ankle in a neutral dorsiflexion position. The index finger was pressed firmly over the bony prominence approximately 3cm proximal to the midpoint of the medial malleolus of the right ankle and will be held for three seconds. Presence of a residual indentation in the area after releasing pressure on the index finger was considered positive for pitting edema.	up to 8 weeks
Change From Baseline in Ankle Circumference at Week 8	Each ankle was marked with a semi-permanent marker at approximately 3 cm proximal to the midpoint of the medial malleolus to aid consistency in the performance of the measurements. Ankle circumference was measured in both ankles at baseline and Week 8 using a tension controlled tape to minimize error.	Baseline and Week 8

Collaborators and Investigators

• Sponsor: Organon and Co

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2011
• Primary Completion (Actual): April 22, 2013
• Study Completion (Actual): April 22, 2013

Study Registration Dates

• First Submitted: January 13, 2011
• First Submitted That Met QC Criteria: January 14, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Hypertension; Essential hypertension; Uncontrolled hypertension; High blood pressure; Uncontrolled high blood pressure; Untreated high blood pressure; Untreated hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Losartan
• Other Study ID Numbers: 0954F-399

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis