Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH)

October 11, 2023 updated by: Novartis

A Prospective, Multinational, Multicenter Trial to Compare the Effects of Amlodipine/Benazepril to Benazepril and Hydrochlorothiazide Combined on the Reduction of Cardiovascular Morbidity and Mortality in Patients With High Risk Hypertension

A comparison study of two combination drugs, amlodipine/benazepril and benazepril/HCTZ to evaluate the effectiveness of the combination on reducing heart disease and death in a high risk hypertensive population.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

11506

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Denmark, Denmark
        • sites in Denmark
  • Finland
      • Finland, Finland
        • sites in Finland
  • Norway
      • Norway, Norway
        • sites in Norway
  • Sweden
      • Sweden, Sweden
        • sites in Sweden
  • United States
    • New Jersey
      • East Hanover, New Jersey, United States, 07936
        • Novartis Pharmaceuticals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • At least 55 years of age.
  • Previously untreated or treated hypertension.
  • For patients >= 60 years, evidence of at least one CV disease or target organ damage, or for patients 55-59 years evidence of at least two CV diseases or target organ damage from two different organ systems as defined in the protocol.

Exclusion Criteria:

  • Allergy to any of the drugs administered in this trial.
  • Current angina pectoris (ie, no anginal event requiring NTG within 1 month prior to Visit 1).
  • Secondary hypertension.
  • Refractory hypertension defined as SBP >= 180 mmHg and/or DBP >= 110 mmHg unresponsive to triple-drug regimens of sympatholytics, diuretics and vasodilators.
  • History of symptomatic heart failure (NYHA classes II-IV) or ejection fraction < 40%.
  • Myocardial infarction, coronary revascularization (CABG or PCI), unstable angina within one month of Visit 1.
  • Stroke or transient ischemic event (TIA) within 3 months of Visit 1.
  • Significant obstructive valvular cardiovascular disease or any valvular disease expected to lead to surgery during the course of the study.
  • Evidence of hepatic disease (AST or ALT values >= 2 X upper limit of normal).
  • Impaired renal function (serum creatinine >= 2.5 mg/dL (221 µmol/L)).
  • Baseline serum potassium of > 5.2 meq/L not on potassium supplements.
  • History of malignancy including leukemia and lymphoma (but not basal cell skin cancer) within the last 5 years.
  • History of clinically significant auto immune disorders such as Systemic Lupus Erythematosus.
  • Significant non-cardiovascular illness or condition likely to result in death prior to trial completion, e.g., major organ transplant (life expectancy <5 years).
  • Significant cardiovascular disease such as an aortic aneurysm ≥ 6 cm, likely requiring surgical intervention during the course of the study.

Other protocol-defined exclusion criteria applied to the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Benazepril/amlodipine
Patients were instructed to take one capsule with water in the morning, except on the morning of their next office visit. On office visit days, study medication was taken after completion of the visit evaluations. Following randomization, all patients were treated at Dose Level 1 for 4 weeks, followed by a forced titration to Dose Level 2 for a subsequent 4 week period. Thereafter, patients were titrated as needed to Dose Level 3 to achieve a target blood pressure of < 140/< 90 mm Hg. For patients with diabetes or chronic kidney disease, investigators were encouraged to use a target blood pressure of 130/80 mm Hg.
Drug: Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1
Benazepril hydrochloride (HCl)/amlodipine besylate 10/5 mg capsules for oral administration once daily.
Drug: Benazepril/amlodipine 40/5 mg - Dose Level 2 from Month 1 to Month 2
Benazepril hydrochloride (HCl)/amlodipine besylate 20/5 mg capsules for oral administration once daily.
Drug: Benazepril/amlodipine 40/10 mg - Dose Level 3 from Month 2 to Month 3 and thereafter
Benazepril hydrochloride (HCl)/amlodipine besylate: 40/10 mg capsules for oral administration once daily. Patients titrated to this dose level had the possibility of subsequent free add-on antihypertensive agents after month 3 based on target blood pressure.
Active Comparator: Benazepril/hydrochlorothiazide
Patients were instructed to take one capsule with water in the morning, except on the morning of their next office visit. On office visit days, study medication was taken after completion of the visit evaluations. Following randomization, all patients were treated at Dose Level 1 for 4 weeks, followed by a forced titration to Dose Level 2 for a subsequent 4 week period. Thereafter, patients were titrated as needed to Dose Level 3 to achieve a target blood pressure of < 140/< 90 mm Hg. For patients with diabetes or chronic kidney disease, investigators were encouraged to use a target blood pressure of 130/80 mm Hg.
Drug: Benazepril/hydrochlorothiazide 20/12.5 mg - Dose Level 1 from Day 1 to Month 1
Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ) 20/12.5 mg capsules for oral administration once daily.
Drug: Benazepril/hydrochlorothiazide 40/12.5 mg - Dose Level 2 from Month 1 to Month 2
Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ) 40/12.5 mg capsules for oral administration once daily.
Drug: Benazepril/hydrochlorothiazide 40/25 mg - Dose Level 3 from Month 2 to Month 3 and thereafter
Benazepril hydrochloride (HCl)/hydrochlorothiazide (HCTZ) 40/25 mg capsules for oral administration once daily. Patients titrated to this dose level had the possibility of subsequent free add-on antihypertensive agents after month 3 based on target blood pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event
Time Frame: For each patient, baseline to time of first CV morbidity or mortality event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])
CV morbidity was defined as non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for unstable angina, resuscitated sudden death, or coronary revascularization procedure. CV mortality was defined as death due to MI, stroke, coronary intervention, congestive heart failure (CHF), sudden cardiac death, or other CV causes.
For each patient, baseline to time of first CV morbidity or mortality event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event
Time Frame: For each patient, baseline to time of first CV morbidity event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])]
Cardiovascular morbidity was defined as including any of the following events: non-fatal MI, non-fatal stroke, hospitalization for unstable angina, resuscitated sudden death, or coronary revascularization procedure (PCI or CABG).
For each patient, baseline to time of first CV morbidity event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])]
Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke
Time Frame: For each patient, baseline to time of first CV mortality event, MI (non-fatal), or stroke (non-fatal) (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])
CV mortality was defined as death due to sudden cardiac death, fatal MI, fatal stroke, coronary intervention, congestive heart failure (CHF), or other CV causes.
For each patient, baseline to time of first CV mortality event, MI (non-fatal), or stroke (non-fatal) (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.])

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis

Investigators

  • Study Chair: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Primary Completion (Actual)

January 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

September 10, 2005

First Submitted That Met QC Criteria

September 10, 2005

First Posted (Estimated)

September 15, 2005

Study Record Updates

Last Update Posted (Actual)

October 24, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCIB002I2301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hypertension

Clinical Trials on Benazepril/amlodipine 20/5 mg - Dose Level 1 from Day 1 to Month 1

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Korea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe