Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 10 for:    lcz696 mri

Personalised Prospective Comparison of ARni With ArB in Patients With Natriuretic Peptide eLEvation (PARABLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04687111
Recruitment Status : Active, not recruiting
First Posted : December 29, 2020
Last Update Posted : May 11, 2021
Sponsor:
Collaborator:
The Heartbeat Trust
Information provided by (Responsible Party):
Mark Ledwidge, St Vincent's University Hospital, Ireland

Brief Summary:
Sacubitril-valsartan, an Angiotensin Receptor Blocker-Neprilysin Inhibitor (ARNI), currently marketed for the management of heart failure, has been shown to reduce cardiovascular morbidity and mortality in stage C heart failure with reduced ejection fraction. In stage C HFpEF, sacubitril-valsartan has also been shown to reduce left atrial volume index measured using echocardiography over a 9 month timeframe. The PARABLE study investigates the hypothesis that sacubitril-valsartan can provide benefits in terms of left atrial structure and function as well as left ventricular structure and function in asymptomatic (stage A/B HFpEF) patients. This is a prospective, randomised, double-blind, double-dummy, phase II study design. The patient population will have hypertension and/or diabetes together with preserved ejection fraction, elevated natriuretic peptide (NP) and abnormal left atrial volume index (LAVI, > 28 mL/m2).

Condition or disease Intervention/treatment Phase
Atrial Remodeling Myocardial Dysfunction Left Ventricular Remodeling Left Ventricular Diastolic Dysfunction Hypertension Cardiovascular Morbidity Fibrosis Myocardial Inflammatory Myopathy Atrial Arrhythmia Drug: Sacubitril-Valsartan Drug: Valsartan Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised, prospective, active comparator, double blind, double dummy, controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind, double-dummy.
Primary Purpose: Prevention
Official Title: A Randomised, Controlled, Double-blind, Double-dummy, Clinical Trial Comparing Sacubitril-Valsartan Versus Valsartan in Asymptomatic, Stage A/B HFpEF Patients With Elevated Natriuretic Peptide and Abnormal LAVI. (Previously NCT02682719)
Actual Study Start Date : December 16, 2015
Estimated Primary Completion Date : June 11, 2021
Estimated Study Completion Date : June 11, 2021


Arm Intervention/treatment
Active Comparator: Control
Valsartan 40mg bid titrated to maximum dose of 160mg bid
Drug: Valsartan
Valsartan is an Angiotensin Receptor Blocker

Experimental: Intervention
Sacubitril/Valsartan 50mg bid titrated to maximum dose of 200mg bid
Drug: Sacubitril-Valsartan
Sacubitril-Valsartan is an Angiotensin Receptor blocker and Neprilysin Inhibitor
Other Names:
  • LCZ696
  • Entresto




Primary Outcome Measures :
  1. Change in Left Atrial Volume Index (LAV/BSA*) [ Time Frame: Baseline-18 months ]
    Measured as left atrial volume (Simpson's method, using a stack of short axis slices across the entire left atrium) indexed to body surface area (*DuBois formula) using Cardiac Magnetic Resonance Imaging (cardiac MRI).


Secondary Outcome Measures :
  1. Change in left ventricular function (E/e') [ Time Frame: Baseline -18 months ]
    Measured average E/e' using Doppler-echocardiography

  2. Change in left atrial volume index (LAV/BSA*) [ Time Frame: Baseline - 9 months ]
    Measured using Doppler Echocardiography between baseline and 9 months. (*BSA calculated using the DuBois formula)

  3. Change in left atrial function measured as total left atrial ejection fraction (LAEF) [ Time Frame: Baseline -18 months ]
    Measured as total LAEF ((LAVmax - LAVmin)/LAVmax, by cardiac MRI

  4. Change in left atrial function measured as left atrial stroke volume index [ Time Frame: Baseline -18 months ]
    Measured as left atrial stroke volume index (LAVmax - LAVmin)/BSA (measured using Du Bois formula), or LAVimax-LAVimin by cardiac MRI

  5. Change in left ventricular structure measured as LVMi [ Time Frame: Baseline -18 months ]
    Measured using left ventricular mass index (LVMi), indexed to BSA (calculated using the DuBois formula) using cardiac MRI

  6. Change in left ventricular function (LVEF) [ Time Frame: Baseline -18 months ]
    Measured as left ventricular ejection fraction (LVEF) using cardiac MRI

  7. Change in measures of vascular compliance (pulse pressure) [ Time Frame: Baseline -18 months ]
    Measured using pulse pressure calculated from 24 hour ABPM measurements

  8. Change in natriuretic peptide biomarker profile [ Time Frame: Baseline -18 months ]
    Defined as log-transformed NT-proBNP

  9. Time to first all cardiovascular death and major adverse cardiac events (MACE) requiring hospitalisation over 18 months [ Time Frame: Baseline - 18 months ]
    MACE includes arrythmia (including atrial fibrillation/flutter), transient ischaemic attack, stroke, valvular heart disease, myocardial infarction, peripheral or pulmonary thrombosis/embolus or heart failure

  10. Change in Left Atrial Volume Index (LAVi) analysed per protocol. [ Time Frame: Baseline - 18 months ]
    Measured as left atrial volume (Simpson's method, using a stack of short axis slices across the entire left atrium) indexed to body surface area (DuBois formula) using Cardiac Magnetic Resonance Imaging (cardiac MRI)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 40yrs with cardiovascular risk factor(s) including at least one of:

    1. History of hypertension (medicated for greater than one month);
    2. History of diabetes;
  2. Elevated NP: Elevated NP: BNP between 20 and 280pg/ml or NT-proBNP values between 100 pg/ml and 1,000 pg/ml within 6 months prior to screening or at screening
  3. LAVI > 28 mL/m2 obtained during Doppler Echocardiography within 6 months prior to screening or at screening
  4. Subjects must give written informed consent to participate in the study and before any study related assessments are performed.

Exclusion Criteria:

  1. A history of heart failure.
  2. Asymptomatic left ventricular systolic dysfunction defined as LVEF <50% on most recent measurement.
  3. Systolic blood pressure <100mmHg
  4. Persistent atrial fibrillation.
  5. History of hypersensitivity, allergy or intolerance to LCZ696, ARB or neprilysin therapy or to any of the excipients or other contraindication to their use.
  6. Previous history of intolerance to recommended target doses for ARBs
  7. Subjects who require treatment with both an ACE inhibitor and an ARB
  8. Presence of haemodynamically significant mitral and /or aortic valve disease.
  9. Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
  10. Conditions that are expected to compromise survival over the study period.
  11. Serum potassium level > 5.2 mmol/L at screening.
  12. Severe renal insufficiency (eGFR <30 mL per minute per 1.73 m2).
  13. Hepatic dysfunction (Any LFT > 3 times the upper limit of normal (ULN))
  14. Concomitant use of aliskiren
  15. History of angioedema.
  16. History or evidence of drug or alcohol abuse within the last 12 months
  17. Malignancy or presence of any other disease with a life expectancy of < 2 years
  18. Women who are pregnant, breast-feeding, or women of child bearing potential not using estro-progestative oral or intra-uterine contraception or implants, or women using estro-progestative oral or intra-uterine contraception or implants but who consider stopping it during the planned duration of the study. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. (Contraception must be continued for one week following discontinuation of study drug).
  19. Concomitant participation in other intervention trials
  20. Participation in any investigational drug trial within one month of visit 1.
  21. Refusal to provide informed consent
  22. Subjects with contraindications to MRI

    1. Brain aneurysm clip
    2. Implanted neural stimulator
    3. Implanted cardiac pacemaker or defibrillator
    4. Cochlear implant
    5. Ocular foreign body (e.g. metal shavings)
    6. Other implanted medical devices: (e.g. Swan-Ganz catheter)
    7. Insulin pump
    8. Metal shrapnel or bullet.
  23. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including but not limited to any of the following:

    1. History of major gastrointestinal tract surgery including gastrectomy, gastroenterostomy, or bowel resection.
    2. Inflammatory bowel disease during the 12 months prior to Visit 1.
    3. Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
    4. Evidence of hepatic disease as determined by any one of the following: SGOT or SGPT values exceeding 3 x ULN at Visit 1, a history of hepatic encephalopathy, a history of oesophageal varices, or a history of portocaval shunt.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04687111


Locations
Layout table for location information
Ireland
The STOP-HF Service, St Michael's Hosptial
Dun Laoghaire, Co Dublin, Ireland
St Vincents University Hospital
Dublin, Ireland, Dublin 4
Sponsors and Collaborators
Mark Ledwidge
The Heartbeat Trust
Investigators
Layout table for investigator information
Study Director: Fiona Ryan, Co-Investigator, PhD Heartbeat Trust, 3 Crofton Terrace, Dun Laoghaire, Co Dublin
  Study Documents (Full-Text)

Documents provided by Mark Ledwidge, St Vincent's University Hospital, Ireland:
Informed Consent Form  [PDF] February 13, 2019

Publications:

Layout table for additonal information
Responsible Party: Mark Ledwidge, Research Director, STOP-HF Unit, St Vincent's University Hospital, Ireland
ClinicalTrials.gov Identifier: NCT04687111    
Obsolete Identifiers: NCT02682719
Other Study ID Numbers: HBT-PTCL-01, SVUH-2015-002
2015-002928-53 ( EudraCT Number )
First Posted: December 29, 2020    Key Record Dates
Last Update Posted: May 11, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Mark Ledwidge, St Vincent's University Hospital, Ireland:
Natriuretic peptide
Atrial remodelling
Atrial cardiomyopathy
Asymptomatic left ventricular diastolic dysfunction
Preserved ejection fraction
Myocardial fibrosis
Myocardial inflammation
Ventricular dysfunction
Additional relevant MeSH terms:
Layout table for MeSH terms
Sacubitril and valsartan sodium hydrate drug combination
Myositis
Ventricular Dysfunction, Left
Fibrosis
Ventricular Remodeling
Atrial Remodeling
Cardiovascular Diseases
Pathologic Processes
Heart Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Pathological Conditions, Anatomical
Ventricular Dysfunction
Valsartan
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action