PIE II: Pharmacological Intervention in the Elderly II

NCT00123955 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: AG0030R01AG0189152R01AG018915-05
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine whether spironolactone will improve exercise tolerance and quality of life in elderly patients with heart failure preserved ejection fraction (HFPEF).

Conditions

Diastolic Heart Failure; Heart Failure, Congestive

Outcome Measures

Primary Outcomes (2)

• Exercise Intolerance

  Peak exercise VO2

  Baseline, 4 and 9 months

• Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire-total Score

  The Minnesota Living with Heart Failure Questionnaire (MLHF) is a self-administered disease-specific questionnaire for patients with Heart Failure, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL), as well as scores for two dimensions, physical (8 items, range 0-40) and emotional (5 items, range 0-25). The other eight items (of the total of 21) are only considered for the calculation of the total score. Scale of 0-105:The higher the score the worse the heart failure related Quality of Life.

  Baseline, 4 and 9 months

Secondary Outcomes (2)

• Concentric Left Ventricular Remodeling

  Baseline, 9 month

• Left Ventricular Diastolic Stiffness

  Baseline, 4 month and 9 month

Study Arms (2)

1

EXPERIMENTAL

Spironolactone

Drug: Spironolactone

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Spironolactone DRUG

25mg tablet daily for 9 months

Also known as: Aldactone

1

Placebo DRUG

Placebo tablet daily for 9 months

2

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory
• Medically stable
• Ages 60 or older
• Diagnosis of diastolic heart failure

You may not qualify if:

• Valvular heart disease
• Significant change in cardiac medication within the past 4 weeks
• Uncontrolled hypertension
• Recent or debilitating stroke
• Cancer or other noncardiovascular conditions with life expectancy less than 2 years
• Anemia
• Elevated serum potassium
• Renal insufficiency
• Psychiatric disease (uncontrolled major psychoses, depression, dementia, or personality disorder)
• Allergy to spironolactone; currently taking spironolactone or any aldosterone antagonist
• Plans to leave area within 1 year
• Refuses informed consent
• Failure to pass screening tests: pulmonary function, echocardiogram, or exercise
• Contra-indications to magnetic resonance imaging \[MRI\] (indwelling metal-containing prosthesis; pacemaker or defibrillator; history of welding occupation; uncontrollable claustrophobia)

Sponsors & Collaborators

• Wake Forest University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (8)

• Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT, Brosnihan B, Morgan TM, Stewart KP. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 2002 Nov 6;288(17):2144-50. doi: 10.1001/jama.288.17.2144.

  PMID: 12413374 BACKGROUND

• Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol. 1991 Apr;17(5):1065-72. doi: 10.1016/0735-1097(91)90832-t.

  PMID: 2007704 BACKGROUND

• Kitzman DW, Gardin JM, Gottdiener JS, Arnold A, Boineau R, Aurigemma G, Marino EK, Lyles M, Cushman M, Enright PL; Cardiovascular Health Study Research Group. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol. 2001 Feb 15;87(4):413-9. doi: 10.1016/s0002-9149(00)01393-x.

  PMID: 11179524 BACKGROUND

• Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000 Nov 28;102(22):2700-6. doi: 10.1161/01.cir.102.22.2700.

  PMID: 11094035 BACKGROUND

• Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. doi: 10.1056/NEJM199909023411001.

  PMID: 10471456 BACKGROUND

• Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zeni P, Caruso B, Zardini P. Relation of aldosterone "escape" despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2002 Feb 15;89(4):403-7. doi: 10.1016/s0002-9149(01)02261-5.

  PMID: 11835920 BACKGROUND

• Kitzman DW, Herrington DM, Brubaker PH, Moore JB, Eggebeen J, Haykowsky MJ. Carotid arterial stiffness and its relationship to exercise intolerance in older patients with heart failure and preserved ejection fraction. Hypertension. 2013 Jan;61(1):112-9. doi: 10.1161/HYPERTENSIONAHA.111.00163. Epub 2012 Nov 12.

  PMID: 23150511 BACKGROUND

• Daniel KR, Wells G, Stewart K, Moore B, Kitzman DW. Effect of aldosterone antagonism on exercise tolerance, Doppler diastolic function, and quality of life in older women with diastolic heart failure. Congest Heart Fail. 2009 Mar-Apr;15(2):68-74. doi: 10.1111/j.1751-7133.2009.00056.x.

  PMID: 19379452 BACKGROUND

MeSH Terms

Conditions

Heart Failure, Diastolic; Heart Failure

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Dalane Kitzman
• Organization: Wake Forest Baptist Health

dkitzman@wakehealth.edu

336-716-3274

Study Officials

• Dalane W. Kitzman, MD

  Professor of Internal Medicine, Cardiology, Director of Echocardiography, Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2005
• First Posted: July 26, 2005
• Study Start: April 1, 2005
• Primary Completion: June 1, 2009
• Study Completion: December 1, 2012
• Last Updated: February 27, 2019
• Results First Posted: February 23, 2015

Record last verified: 2019-02

Locations

US (1)