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Chronic Heart Failure (CHF)Phase 3PERSPECTIVENCT02884206

Efficacy and Safety of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction

A Phase 3 study testing LCZ696 and Valsartan in people with Chronic Heart Failure (CHF), run by Novartis Pharmaceuticals at 135 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study was a multi-center, randomized, double-blind, parallel group, active comparator trial designed to evaluate the overall effect of LCZ696 compared to valsartan on cognitive function as assessed by the CogState comprehensive cognitive battery in patients with Heart failure and preserved ejection fraction… Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Chronic Heart Failure (CHF)
What is being tested?
LCZ696 and Valsartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
592 participants
Where
135 sitesin 20 countries
Study dates
23 Nov 2016to 16 May 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Chronic heart failure with current symptoms NYHA class II-IV
  • Left ventricular ejection fraction > 40%
  • NT-proBNP >= 125 pg/mL at screening visit
  • Patient with evidence of adequate functioning to complete study assessments

Who cannot join

  • Patients with acute decompensated heart failure requiring augmented therapy with diuretics, vasodilators and/or inotropic drugs
  • Acute coronary syndrome (including myocardial infarction (MI)), cardiac surgery, other major CV surgery, or urgent percutaneous coronary intervention (PCI), carotid surgery or carotid angioplasty, history of stroke or transient ischemic attack within the 3 months prior to Screening visit or an elective PCI within 30 days prior to Screening visit
  • Patients with history of hereditary or idiopathic angioedema or angioedema related to previous ACEi or ARB therapies
  • Patients who require treatment with 2 or more of the following: an ACEi, an ARB or a renin inhibitor
  • Patients with one of the following:
  • Patients with serum potassium >5.2 mmol/L (mEq/L) at Screening visit
Show all 19Show fewer
  • Patients with serum potassium >5.4 mmol/L (mEq/L) at any visit during run-in treatment period or at randomization visit
  • Systolic blood pressure (SBP) ≥180 mmHg at Screening visit, or
  • SBP <110 mmHg at Screening visit, or
  • SBP <100 mmHg or symptomatic hypotension as determined by the investigator at Visit 103 or at randomization visit
  • Body mass index (BMI) >45 kg/m^2
  • Patients with
  • known pericardial constriction, genetic hypertrophic cardiomyopathy, infiltrative cardiomyopathy
  • hemodynamically significant obstructive valvular disease
  • Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or flutter with a resting ventricular rate >110 beats per minute
  • Inability to perform cognitive battery or other study evaluations based on significant motor (e.g. hemiplegia, muscular-skeletal injury) or sensory (blindness, decreased or uncorrected visual or auditory acuity) skill
  • Clinically significant cerebral pathology for example large cerebral aneurysm or space occupying lesion that may impact cognition as assessed by central MRI reader
  • Mini mental state examination score less than 24 at screening
  • Patients with a clinical diagnosis of Alzheimer's disease or other dementia syndromes or any indication for or current treatment with cholinesterase inhibitors and/or another prescription AD treatment (e.g. memantine).

Trial locations and contacts

135 sites in 20 countries.

135 sites in 20 countries

United States52 sites

  • Novartis Investigative Site

    Andalusia, Alabama, 36420

  • Novartis Investigative Site

    Baltimore, Maryland, 21229

  • Novartis Investigative Site

    Beverly Hills, California, 90211

  • Novartis Investigative Site

    Buffalo, New York, 14215

  • Novartis Investigative Site

    Cincinnati, Ohio, 45219

  • Novartis Investigative Site

    Clearwater, Florida, 33756

  • Novartis Investigative Site

    Dallas, Texas, 75226

  • Novartis Investigative Site

    Dallas, Texas, 75235

  • Novartis Investigative Site

    Danbury, Connecticut, 06810

  • Novartis Investigative Site

    Edgewater, Florida, 32132

  • Novartis Investigative Site

    Elmer, New Jersey, 08318

  • Novartis Investigative Site

    Eunice, Louisiana, 70535

  • Novartis Investigative Site

    Fort Mill, South Carolina, 29707

  • Novartis Investigative Site

    Fresno, California, 93720

  • Novartis Investigative Site

    Gastonia, North Carolina, 28054

  • Novartis Investigative Site

    Glendale, Arizona, 85306

  • Novartis Investigative Site

    Gonzales, Texas, 78629

  • Novartis Investigative Site

    Hollywood, Florida, 33312

  • Novartis Investigative Site

    Homestead, Florida, 33030

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Inverness, Florida, 34452

  • Novartis Investigative Site

    Jacksonville Beach, Florida, 32050

  • Novartis Investigative Site

    Kalispell, Montana, 59901 3158

  • Novartis Investigative Site

    Loma Linda, California, 92357

  • Novartis Investigative Site

    Lombard, Illinois, 60148

  • Novartis Investigative Site

    Long Beach, California, 90806

  • Novartis Investigative Site

    Lufkin, Texas, 75904

  • Novartis Investigative Site

    Mesa, Arizona, 85206

  • Novartis Investigative Site

    Miami, Florida, 33133

  • Novartis Investigative Site

    Miami, Florida, 33144

  • Novartis Investigative Site

    Miami, Florida, 33176

  • Novartis Investigative Site

    Naples, Florida, 34102

  • Novartis Investigative Site

    Newport Beach, California, 92663

  • Novartis Investigative Site

    Oregon City, Oregon, 97045

  • Novartis Investigative Site

    Phoenix, Arizona, 85004

  • Novartis Investigative Site

    Port Orange, Florida, 32127

  • Novartis Investigative Site

    Reno, Nevada, 89502

  • Novartis Investigative Site

    Rock Hill, South Carolina, 29732

  • Novartis Investigative Site

    Saginaw, Michigan, 48601

  • Novartis Investigative Site

    San Antonio, Texas, 78229

  • Novartis Investigative Site

    Santa Ana, California, 92704

  • Novartis Investigative Site

    Santa Ana, California, 92705

  • Novartis Investigative Site

    Springfield, Illinois, 62701

  • Novartis Investigative Site

    Springfield, Oregon, 97477

  • Novartis Investigative Site

    St Louis, Missouri, 63110

  • Novartis Investigative Site

    Summerville, South Carolina, 29485

  • Novartis Investigative Site

    Sun City West, Arizona, 85375

  • Novartis Investigative Site

    Tacoma, Washington, 98405

  • Novartis Investigative Site

    Tampa, Florida, 33612

  • Novartis Investigative Site

    Topeka, Kansas, 66606

  • Novartis Investigative Site

    Torrance, California, 90503

  • Novartis Investigative Site

    Tucson, Arizona, 85723

Other trials in United States

Germany16 sites

  • Novartis Investigative Site

    Berlin, 10367

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Bielefeld, 33604

  • Novartis Investigative Site

    Bitburg, 54634

  • Novartis Investigative Site

    Buch, 13125

  • Novartis Investigative Site

    Cologne, 50937

  • Novartis Investigative Site

    Cologne, 51065

  • Novartis Investigative Site

    Dessau, 06846

  • Novartis Investigative Site

    Dresden, Saxony, 01099

  • Novartis Investigative Site

    Dresden, 01277

  • Novartis Investigative Site

    Elsterwerda, 04910

  • Novartis Investigative Site

    Frankfurt, 60594

  • Novartis Investigative Site

    Regensburg, Bavaria, 93053

  • Novartis Investigative Site

    Ulm, 89077

  • Novartis Investigative Site

    Wuppertal, 42109

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

United Kingdom9 sites

  • Novartis Investigative Site

    Axbridge, Somerset, BS26 2BJ

  • Novartis Investigative Site

    Birmingham, B16 8QQ

  • Novartis Investigative Site

    Bournemouth, BH7 7DW

  • Novartis Investigative Site

    Cardiff, Wales, CF5 4AD

  • Novartis Investigative Site

    East Yorkshire, HU16 5JQ

  • Novartis Investigative Site

    Harrow, HA1 3UJ

  • Novartis Investigative Site

    Liverpool, L9 7AL

  • Novartis Investigative Site

    Newport, NP20 2UB

  • Novartis Investigative Site

    Stevenage, SG1 4AB

Other trials in United Kingdom

Italy8 sites

  • Novartis Investigative Site

    Ancona, AN, 60128

  • Novartis Investigative Site

    Bergamo, BG, 24127

  • Novartis Investigative Site

    Cona, FE, 44100

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Modena, MO, 41100

  • Novartis Investigative Site

    Pisa, PI, 56124

  • Novartis Investigative Site

    Pozzilli, IS, 86077

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Poland7 sites

  • Novartis Investigative Site

    Bialystok, 15 276

  • Novartis Investigative Site

    Katowice, 40-645

  • Novartis Investigative Site

    Krakow, Maloposkie, 31271

  • Novartis Investigative Site

    Krakow, 31 202

  • Novartis Investigative Site

    Lodz, Łódź Voivodeship, 90 549

  • Novartis Investigative Site

    Tarnów, Lesser Poland Voivodeship, 33-100

  • Novartis Investigative Site

    Warsaw, 02-097

Other trials in Poland

Spain7 sites

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    San Sebastián de los Reyes, Madrid, 28702

  • Novartis Investigative Site

    Valencia, Valencia, 46010

  • Novartis Investigative Site

    Valencia, 46026

  • Novartis Investigative Site

    Zaragoza, 50009

Other trials in Spain

Argentina5 sites

  • Novartis Investigative Site

    Buenos Aires, ARG, C1405BCK

  • Novartis Investigative Site

    CABA, Buenos Aires, 1407

  • Novartis Investigative Site

    CABA, Buenos Aires F.D., C1179AAB

  • Novartis Investigative Site

    Ciudad Autonoma de Bs As, Buenos Aires, C1119ACN

  • Novartis Investigative Site

    Ramos Mejía, Buenos Aires, B1704ETD

Other trials in Argentina

Russia5 sites

  • Novartis Investigative Site

    Moscow, 127644

  • Novartis Investigative Site

    Saint Petersburg, 196601

  • Novartis Investigative Site

    Saint Petersburg, 197022

  • Novartis Investigative Site

    Saint Petersburg, 199106

  • Novartis Investigative Site

    Saratov, 410012

Other trials in Russia

Australia4 sites

  • Novartis Investigative Site

    Bedford Park, South Australia, 5042

  • Novartis Investigative Site

    Chemside, Queensland, 4032

  • Novartis Investigative Site

    Geelong, Victoria, 3220

  • Novartis Investigative Site

    Milton, Queensland, 4064

Other trials in Australia

South Korea3 sites

  • Novartis Investigative Site

    Seongnam-si, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Wŏnju, Gangwon-do, 26426

Other trials in South Korea

Taiwan3 sites

  • Novartis Investigative Site

    Tainan, 70403

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taipei, 11217

Other trials in Taiwan

Bulgaria2 sites

  • Novartis Investigative Site

    Sofia, BGR, 1407

  • Novartis Investigative Site

    Sofia, 1431

Other trials in Bulgaria

Canada2 sites

  • Novartis Investigative Site

    Greenfield Park, Quebec, J4V 2G8

  • Novartis Investigative Site

    Hamilton, Ontario, L8L 2X2

Other trials in Canada

Croatia2 sites

  • Novartis Investigative Site

    Rijeka, 51000

  • Novartis Investigative Site

    Zagreb, 10000

Other trials in Croatia

France2 sites

  • Novartis Investigative Site

    Paris, 75013

  • Novartis Investigative Site

    Tourcoing, 59208

Other trials in France

Lithuania2 sites

  • Novartis Investigative Site

    Kaunas, LTU, LT 50161

  • Novartis Investigative Site

    Vilnius, LT-08661

Other trials in Lithuania

Netherlands2 sites

  • Novartis Investigative Site

    's-Hertogenbosch, 5223 GZ

  • Novartis Investigative Site

    Amsterdam, 1081 HV

Other trials in Netherlands

Turkey (Türkiye)2 sites

  • Novartis Investigative Site

    Meselik, Eskişehir, 26480

  • Novartis Investigative Site

    Sivas, 58140

Other trials in Turkey (Türkiye)

Belgium1 site

  • Novartis Investigative Site

    Aalst, 9300

Other trials in Belgium

Switzerland1 site

  • Novartis Investigative Site

    Basel, 4031

Other trials in Switzerland

About this study

Official title: A Multicenter, Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of LCZ696 Compared to Valsartan on Cognitive Function in Patients With Chronic Heart Failure and Preserved Ejection Fraction

This study was a multi-center, randomized, double-blind, parallel group, active comparator trial designed to evaluate the overall effect of LCZ696 compared to valsartan on cognitive function as assessed by the CogState comprehensive cognitive battery in patients with Heart failure and preserved ejection fraction (HFpEF).

Read the detailed description

The Screening epoch of approximately 3 weeks was used to assess eligibility. Eligible patients then entered the single-blind treatment run-in epoch (Active Run-In Epoch), which was designed to assess patient's tolerability to study drug and to determine patients who were likely to stay on study drug for the duration of the trial. The treatment run-in consisted of valsartan 40 mg bid (if necessary), followed by valsartan 80 mg bid, and then followed by LCZ696 100 mg bid, over 3 to 8 weeks duration. Patients unable to tolerate either valsartan or LCZ696 at the prescribed doses during the treatment run-in were not eligible for randomization and were discontinued from the study.

At randomization (Visit 199/201), eligible patients were randomized 1:1 to receive either LCZ696 200 mg bid or valsartan 160 mg bid (double-blind period).

Patients who terminated the study early were expected, and were encouraged, to attend all the protocol specified study visits, to perform all measurements as stipulated in the visit schedule and to remain in follow up for the duration of the trial.

Being tested
LCZ696, Valsartan, Placebo of LCZ696, Placebo of Valsartan
Keywords
heart failure, cognition, positron emission tomography, magnetic resonance imaging, LCZ696, valsartan, Chronic heart failure, CHF
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LCZ696Drug

    LCZ696 50, 100, and 200 mg tablets taken orally twice daily with matching placebo for valsartan

  • ValsartanDrug

    Valsartan 40, 80, and 160 mg tablets taken orally twice daily with matching placebo for LCZ696

  • Placebo of LCZ696Drug

    Placebo to match LCZ696 50 mg, 100 mg, and 200 mg tablets

  • Placebo of ValsartanDrug

    Placebo to match valsartan 40 mg, 80 mg, and 160 mg tablets

Study groups in NCT02884206
Study groupRoleWhat they receive
LCZ696 200 mg bidExperimentalPatients who were able to tolerate the treatment during the single-blind treatment run-in epoch. Following the run-in period, patients randomized in this arm were given LCZ696 at 200 mg twice daily for three years
Receives: Drug: LCZ696; Drug: Placebo of Valsartan
Valsartan 160 mg bidActive comparatorPatients who were able to tolerate the treatment during the single-blind treatment run-in epoch. Following the run-in period, patients randomized in this arm were given valsartan at 160 mg twice daily for three years.
Receives: Drug: Valsartan; Drug: Placebo of LCZ696

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in the CogState Global Cognitive Composite Score (GCCS)

    The CogState cognitive battery was composed of 7 tests, which were administered electronically by the patients at scheduled visits. For each test, a standardized z-score was calculated. The GCCS was the average of the non-missing individual test z-scores. A higher score indicated better cognitive function.

    CogState GCCS changes from baseline (randomization) were analyzed using a repeated measures ANCOVA in which treatment, age stratification factor, Mini mental state examination stratification factor, education level, Apolipoprotein E ε4 allele status, cerebrovascular disease burden at screening, visit and treatment-by-visit interaction are included as fixed-effect factor, and baseline (randomization) GCCS and visit-by- baseline GCCS as covariates with a common unstructured covariance matrix among visits between treatment groups. The analysis was based on a direct likelihood method with an assumption of Missing at random.

    Measured: Baseline, month 36

Secondary outcomes (3)

  1. Change From Baseline in Cortical Composite Standardized Uptake Value Ratio (SUVr)

    The effects of LCZ696 compared to valsartan on Aβ deposition in the brain over 3 years were evaluated in a subset of patients using amyloid positron emission tomography (PET) imaging by assessing the change from baseline in cortical composite SUVr. PET imaging was performed at selected PET-capable centers on all eligible patients participating in the substudy. Sites with patients performing the PET scan were a subset of the overall patient population and overall sites for the study.

    Change from baseline to 3 years was analyzed based on an ANCOVA model with treatment, age, MMSE, amyloid status (+ve/-ve) stratification factors, region, APOE4 status and cerebrovascular disease burden as fixed effects, with baseline SUVr and treatment-by-baseline SUVr interaction as covariates for each of these imputed datasets. Results were obtained by applying Rubin's rules on the estimates from the imputed datasets.

    Measured: Baseline, month 36

  2. Change From Baseline in Individual Cognitive Domains

    The effects of LCZ696 compared to valsartan on the individual cognitive domains (memory, executive function, and attention) over 3 years were evaluated by assessing the individual components of the CogState cognitive battery. Composite scores for the 3 individual cognitive domains were generated by combining the standardized z-scores of selected tests from the CogState cognitive battery. Each composite score was the average of the non-missing individual test z-scores. A higher score indicated better cognitive function.

    Measured: Baseline, month 36

  3. Change From Baseline in the Summary Score of the Instrumental Activities of Daily Living (IADL)

    The effects of LCZ696 compared to valsartan on the changes in IADL over 3 years were evaluated by as assessing the Functional activities questionnaire (FAQ) summary scores.

    The FAQ is a 30-point questionnaire that is made up of 10 questions that reflect a patient's ability to perform activities of daily living and to function independently. A score of 0 represents no impairment and a score of 30 represents severe impairment.

    Measured: Baseline, month 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2016 (estimated)
  2. Study start23 Nov 2016
  3. Primary completion16 May 2022
  4. Study completion16 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
592 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02884206
Sponsor's protocol ID
CLCZ696B2320
Other IDs
2016-001254-17, 2016
Acronym
PERSPECTIVE
Status last verified
Jul 2024
First submitted
25 Aug 2016
Last updated
6 Aug 2024
Data monitoring committee
Yes
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LCZ696 and Valsartan in people with Chronic Heart Failure (CHF), run by Novartis Pharmaceuticals at 135 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 135 sites in United States, Germany, United Kingdom, Italy, Poland and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the CogState Global Cognitive Composite Score (GCCS) (time frame: Baseline, month 36). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02884206.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.

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