NCT00795912

Brief Summary

Inflammation and fibrosis may be important contributors to worsening heart failure. As well as lowering cholesterol, statins are also known to reduce inflammatory markers such as C-reactive protein which are elevated in severe heart failure. Therefore, this project will evaluate the benefit, if any, of statins on markers of heart structure and function, on inflammatory markers and markers of fibrosis in patients with normal cholesterol.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
56

participants targeted

Target at P25-P50 for phase_4 heart-failure

Timeline
Completed

Started May 2003

Longer than P75 for phase_4 heart-failure

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2003

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2005

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2008

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

November 19, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 21, 2008

Completed
Last Updated

November 21, 2008

Status Verified

November 1, 2008

Enrollment Period

2.5 years

First QC Date

November 19, 2008

Last Update Submit

November 20, 2008

Conditions

Heart Failure

Keywords

Systolic heart failureHMG CoA reductase inhibitorsB-type natriuretic peptideInflammationMyocardial collagen turnover

Outcome Measures

Primary Outcomes (1)

  • hsCRP, TNF-alpha, IL-6

    6 months

Secondary Outcomes (1)

  • B-Type Natriuretic Peptide Markers of collagen turnover

    6 months

Study Arms (2)

1

ACTIVE COMPARATOR

Atorvastatin titrated from 10-40 mg/day over 3 months and maintained at 40mg/day for a further 3 months

Drug: Atorvastatin

2

NO INTERVENTION

Usual medical care of heart failure

Interventions

AtorvastatinDRUG

atorvastatin titrated from 10-40 mg/day over 3 months and maintained at 40mg/day for a further 3 months

Also known as: Lipitor
1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Mild to moderate HF (NYHA class II-III) of any aetiology and documented left ventricular systolic dysfunction (LVEF \< 45%) by echocardiography within 3 months of randomization. These patients were clinically stable, on optimal HF medical therapy which had remained unaltered for at least four weeks prior to recruitment. All had normal fasting total cholesterol.

You may not qualify if:

  • Those receiving lipid lowering agents; those with absolute or relative contraindications to statins; those with known chronic inflammatory conditions; patients with medical conditions requiring anti-inflammatory or immuno-suppressive therapies.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Heart Failure Unit, St Vincents University Hospital

Dublin, Co Dublin, 4, Ireland

Location

Related Publications (19)

  • Cleland JG, Swedberg K, Poole-Wilson PA. Successes and failures of current treatment of heart failure. Lancet. 1998 Aug;352 Suppl 1:SI19-28. doi: 10.1016/s0140-6736(98)90015-0. No abstract available.

    PMID: 9736476BACKGROUND

  • Clearfield MB. Statins: balancing benefits, efficacy and safety. Expert Opin Pharmacother. 2002 May;3(5):469-77. doi: 10.1517/14656566.3.5.469.

    PMID: 11996626BACKGROUND

  • Braunstein JB, Cheng A, Cohn G, Aggarwal M, Nass CM, Blumenthal RS. Lipid disorders: justification of methods and goals of treatment. Chest. 2001 Sep;120(3):979-88. doi: 10.1378/chest.120.3.979.

    PMID: 11555537BACKGROUND

  • Krum H, McMurray JJ. Statins and chronic heart failure: do we need a large-scale outcome trial? J Am Coll Cardiol. 2002 May 15;39(10):1567-73. doi: 10.1016/s0735-1097(02)01827-2.

    PMID: 12020481BACKGROUND

  • Kjekshus J. Debate: Statins should be used in patients with heart failure. Curr Control Trials Cardiovasc Med. 2001;2(6):268-270. doi: 10.1186/cvm-2-6-268.

    PMID: 11806812BACKGROUND

  • Kronmal RA, Cain KC, Ye Z, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993 May 10;153(9):1065-73.

    PMID: 8481074BACKGROUND

  • Tavazzi L, Tognoni G, Franzosi MG, Latini R, Maggioni AP, Marchioli R, Nicolosi GL, Porcu M; GISSI-HF Investigators. Rationale and design of the GISSI heart failure trial: a large trial to assess the effects of n-3 polyunsaturated fatty acids and rosuvastatin in symptomatic congestive heart failure. Eur J Heart Fail. 2004 Aug;6(5):635-41. doi: 10.1016/j.ejheart.2004.03.001.

    PMID: 15302013BACKGROUND

  • Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis. Lancet. 2000 Sep 9;356(9233):930-3. doi: 10.1016/S0140-6736(00)02690-8.

    PMID: 11036910BACKGROUND

  • Alonso-Martinez JL, Llorente-Diez B, Echegaray-Agara M, Olaz-Preciado F, Urbieta-Echezarreta M, Gonzalez-Arencibia C. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail. 2002 Jun;4(3):331-6. doi: 10.1016/s1388-9842(02)00021-1.

    PMID: 12034159BACKGROUND

  • Gullestad L, Kjekshus J, Damas JK, Ueland T, Yndestad A, Aukrust P. Agents targeting inflammation in heart failure. Expert Opin Investig Drugs. 2005 May;14(5):557-66. doi: 10.1517/13543784.14.5.557.

    PMID: 15926863BACKGROUND

  • Riesen WF, Engler H, Risch M, Korte W, Noseda G. Short-term effects of atorvastatin on C-reactive protein. Eur Heart J. 2002 May;23(10):794-9. doi: 10.1053/euhj.2001.2967.

    PMID: 12009719BACKGROUND

  • Weber KT, Sun Y, Tyagi SC, Cleutjens JP. Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. J Mol Cell Cardiol. 1994 Mar;26(3):279-92. doi: 10.1006/jmcc.1994.1036.

    PMID: 8028011BACKGROUND

  • Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999 Jan;79(1):215-62. doi: 10.1152/physrev.1999.79.1.215.

    PMID: 9922372BACKGROUND

  • Bujak M, Ren G, Kweon HJ, Dobaczewski M, Reddy A, Taffet G, Wang XF, Frangogiannis NG. Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling. Circulation. 2007 Nov 6;116(19):2127-38. doi: 10.1161/CIRCULATIONAHA.107.704197. Epub 2007 Oct 22.

    PMID: 17967775BACKGROUND

  • Querejeta R, Lopez B, Gonzalez A, Sanchez E, Larman M, Martinez Ubago JL, Diez J. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation. 2004 Sep 7;110(10):1263-8. doi: 10.1161/01.CIR.0000140973.60992.9A. Epub 2004 Aug 16.

    PMID: 15313958BACKGROUND

  • Martos R, Baugh J, Ledwidge M, O'Loughlin C, Conlon C, Patle A, Donnelly SC, McDonald K. Diastolic heart failure: evidence of increased myocardial collagen turnover linked to diastolic dysfunction. Circulation. 2007 Feb 20;115(7):888-95. doi: 10.1161/CIRCULATIONAHA.106.638569. Epub 2007 Feb 5.

    PMID: 17283265BACKGROUND

  • 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: 11094035BACKGROUND

  • Kapoun AM, Liang F, O'Young G, Damm DL, Quon D, White RT, Munson K, Lam A, Schreiner GF, Protter AA. B-type natriuretic peptide exerts broad functional opposition to transforming growth factor-beta in primary human cardiac fibroblasts: fibrosis, myofibroblast conversion, proliferation, and inflammation. Circ Res. 2004 Mar 5;94(4):453-61. doi: 10.1161/01.RES.0000117070.86556.9F. Epub 2004 Jan 15.

    PMID: 14726474BACKGROUND

  • Abulhul E, McDonald K, Martos R, Phelan D, Spiers JP, Hennessy M, Baugh J, Watson C, O'Loughlin C, Ledwidge M. Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide. Clin Ther. 2012 Jan;34(1):91-100. doi: 10.1016/j.clinthera.2011.11.002. Epub 2011 Dec 9.

    PMID: 22154198DERIVED

MeSH Terms

Conditions

Heart FailureHeart Failure, SystolicInflammation

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Study Officials

  • Mark T Ledwidge, PhD

    St Vincent's University Hospital, Ireland

    PRINCIPAL INVESTIGATOR

  • Kenneth M McDonald, MD

    St Vincent's University Hospital, Ireland

    PRINCIPAL INVESTIGATOR

  • Esam Abulhul, MB

    St Vincents University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

November 19, 2008

First Posted

November 21, 2008

Study Start

May 1, 2003

Primary Completion

November 1, 2005

Study Completion

January 1, 2008

Last Updated

November 21, 2008

Record last verified: 2008-11

Locations

IE(1)