Effects of Valsartan vs Amlodipine and Low BP on Kidney Outcomes in Essential Hypertension

NCT06395194 | Completed Phase 3 DMC

• 1 other identifier: OsloUHtheValueTrial
• Study Type: interventional
• Target: 15,313
• Locations: 0 countries
• Sites: N/A

Brief Summary

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial tested the hypothesis that for the same blood-pressure control, valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk. The present study investigates effects of valsartan and amlodipine on pre-specified secondary kidney outcomes.

Conditions

Essential Hypertension

Keywords

Hypertension; Blood pressure; valsartan; amlodipine; kidney disease

Outcome Measures

Primary Outcomes (1)

• Composite cardiac event (mostly myocardial infarction and heart failure hospitalization)

  Composite cardiac events, which included a combination of fatal or non-fatal myocardial infarction, sudden cardiac death, death from revascularization procedures or heart failure, hospitalization for heart failure, and emergency procedures to prevent myocardial infarction

  Up to 6 years

Secondary Outcomes (9)

• End-stage kidney failure

  Up to 6 years

• Worsened kidney function

  Up to 6 years

• All cardiovascular events

  Up to 6 years

• Stroke

  Up to 6 years

• Myocardial infarction

  Up to 6 years

Study Arms (2)

Valsartan

ACTIVE COMPARATOR

Treatment based on the ARB valsartan

Drug: Cardiac outcomes on treatment with valsartan

Amlodipine

ACTIVE COMPARATOR

Treatment based on the CCB amlodipine

Drug: Cardiac outcomes on treatment with amlodipine

Interventions

Cardiac outcomes on treatment with valsartan DRUG

Patients who already were on treatment, discontinued their previous antihypertensive medications when randomized to one of the trial's masked study arms (valsartan or amlodipine) without a run-in phase ("rolled over"). Valsartan treatment started at a dosage of 80 mg daily. If BP did not reach \<140/90 mmHg, the valsartan dose was doubled to 160 mg, and then hydrochlorothiazide (12.5 mg and 25 mg daily) and other antihypertensive drugs were added in sequential steps.

Also known as: Angiotensin-receptor blocker

Valsartan

Cardiac outcomes on treatment with amlodipine DRUG

Patients who already were on treatment, discontinued their previous antihypertensive medications when randomized to one of the trial's masked study arms (valsartan or amlodipine) without a run-in phase ("rolled over"). Amlodipine treatment started at 5 mg daily. If BP did not reach \<140/90 mmHg, the amlodipine dose was doubled to 10 mg, and then hydrochlorothiazide (12.5 mg and 25 mg daily) and other antihypertensive drugs were added in sequential steps.

Also known as: Calcium-channel blocker

Amlodipine

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• hypertension, and predefined combinations of risk factors, including:
• age
• male gender
• the presence of electrocardiographic left ventricular hypertrophy (LVH, determined by Cornell voltage-duration product or Sokolow-Lyon voltage criteria with or without a strain pattern)
• serum creatinine ≥150 μmol/l
• proteinuria (positive urine dipstick at two occasions)
• type 2 diabetes mellitus
• verified coronary, cerebrovascular, or peripheral artery disease

You may not qualify if:

• pregnancy
• renal artery stenosis
• myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery during last three months
• medically relevant cardiac valvular disease
• cerebrovascular events last 3 months
• severe hepatic disease
• severe chronic kidney failure (serum creatinine \>3.0 mg/dl, \>265 µmol/L)
• congestive heart failure requiring angiotensin converting enzyme inhibitor (ACEI)
• use of beta-blocker for both coronary artery disease and hypertension

Sponsors & Collaborators

• Oslo University Hospital: lead
• University of Oslo: collaborator

Related Publications (2)

• Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A; VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004 Jun 19;363(9426):2022-31. doi: 10.1016/S0140-6736(04)16451-9.

  PMID: 15207952 RESULT

• Olsen E, Soraas CL, Schmieder RE, Jamerson K, MacDonald TM, Mancia G, Heimark S, Mehlum MH, Liestol K, Larstorp ACK, Mariampillai JE, Mo R, Halvorsen LV, Hoieggen A, Rostrup M, Kjeldsen SE, Weber MA. Low Achieved Systolic Blood Pressure Related to Kidney Protection in Diabetic and Non-Diabetic High-Risk Hypertensive Patients. Am J Hypertens. 2025 Nov 17;38(12):1106-1119. doi: 10.1093/ajh/hpaf093.

  PMID: 40397037 DERIVED

MeSH Terms

Conditions

Essential Hypertension; Hypertension; Kidney Diseases

Interventions

Valsartan; Angiotensin Receptor Antagonists; Amlodipine; Calcium Channel Blockers

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Dihydropyridines; Pyridines; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Cardiovascular Agents; Therapeutic Uses

Study Officials

• Sverre E Kjeldsen, MD, PhD

  University Of Oslo Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Preparation of the two drugs (to compare, valsartan and amlodipine) made identical
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Emeritus

Model Details: Investigator-designed, prospective, multi-national, double-blind, randomized, active-controlled, parallel-group design which was event driven (until accumulated 1450 primary cardiac endpoints)

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: May 2, 2024
• Study Start: September 27, 1997
• Primary Completion: September 5, 2003
• Study Completion: December 5, 2003
• Last Updated: May 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share