Does the Reduction of Total Body Iron Storage (TBIS) Alter Mortality in a Population of Patients With Advanced PVD?

NCT00032357 | Completed Phase 3 DMC

• 1 other identifier: 410
• Study Type: interventional
• Target: 1,277
• Locations: 2 countries
• Sites: 24

Brief Summary

Veterans Affairs Cooperative Study #410, The Iron and Atherosclerosis Trial, FeAST, a 24-hospital prospective randomized single-blinded clinical trial of graded iron reduction was conducted between May 1, 1999 and April 30, 2005, and has now been completed. A total of 1,277 primarily male participants with peripheral arterial disease were entered. The primary outcome was all cause mortality and the secondary outcome combined death plus non-fatal myocardial infarction (MI) and stroke.

Conditions

Atherosclerosis; Intermittent Claudication; Peripheral Vascular Diseases

Keywords

Ferritin reduction; Peripheral Vascular Disease (PVD); phlebotomy; Reduction of Total Body Iron Storage(TBIS); Total Body Iron Storage(TBIS)

Outcome Measures

Primary Outcomes (1)

• Mortality

  The primary objective of this study is to evaluate the effectiveness of a reduction of Total Body Iron Stores (TBIS) in decreasing the rate of all cause mortality in patients with peripheral vascular disease (PVD).

  The minimum follow-up was 3.5 years and maximum follow-up was 6 years

Study Arms (2)

Arm 1

OTHER

Usual care plus Ferritin reduction to a calculated nadir of 25 ng/mL by phlebotomy

Procedure: Ferritin reduction to 25 ng/ml by phlebotomy

Arm 2

NO INTERVENTION

Usual care only; no intervention control

Interventions

Ferritin reduction to 25 ng/ml by phlebotomy PROCEDURE

Arm 1

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males over the age of 21 years and post menopausal (either natural or surgical) females with a diagnosis of intermittent claudication who are not scheduled for major surgery and who can give informed consent will be entered.
• Hematocrit of 30% or greater for females and 35% or greater for males, normal liver function, serum creatinine less than 4 mg/dl. Patients with mild anemia and mild creatinine elevation will be entered (provided the anemia is not due to Fe deficiency found on screening laboratory tests) because such findings are commonly present chronically in PVD.
• Absence of a disturbance in Fe balance (e.g. hemosiderosis from any cause, hemochromatosis, atransferrinemia, PNH, Fe deficiency)
• Absence for at least six months of a disease that has caused bleeding (e.g. peptic ulcer, inflammatory bowel disease, hemorrhagic diathesis )
• Absence of associated neoplasm other than epithelial ( non-melanoma) tumors of skin or other co-morbid condition that is expected to be fatal within one year.
• Absence of an associated obvious inflammatory disorder (e.g. infection, connective tis-sue disease) capable of elevating ferritin levels acutely.
• Patients will not be excluded on the basis of either the existence or severity of either coronary- or cerebrovascular disease, medication use including non-steroidal anti-inflammatory drugs and anticoagulants, coronary angiographic findings, previous history of or possible future need for angioplasty or coronary bypass surgery, or elevated blood pressure.
• Patients must agree to not take any Fe supplements or vitamins while on study.

You may not qualify if:

• \. Patients must have at least one lower extremity and must not be on another experimental therapy protocol for atherosclerotic vascular disease.

Sponsors & Collaborators

• US Department of Veterans Affairs: lead

Study Sites (24)

VA Medical Center, Birmingham

Birmingham, Alabama, 35233, United States

Location

Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock

No. Little Rock, Arkansas, 72114-1706, United States

Location

VA Medical Center, Long Beach

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304-1290, United States

Location

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, 06516, United States

Location

North Florida/South Georgia Veterans Health System

Gainesville, Florida, 32608, United States

Location

James A. Haley Veterans Hospital, Tampa

Tampa, Florida, 33612, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141-5000, United States

Location

VA Medical Center, Lexington

Lexington, Kentucky, 40502, United States

Location

VA Medical Center, Louisville

Louisville, Kentucky, 40206, United States

Location

VA Medical Center, Jamaica Plain Campus

Boston, Massachusetts, 02130, United States

Location

VA Sierra Nevada Health Care System

Reno, Nevada, 89502, United States

Location

VA Stratton Medical Center, Albany

Albany, New York, 12208, United States

Location

New York Harbor HCS

New York, New York, 10010, United States

Location

VA Medical Center, Durham

Durham, North Carolina, 27705, United States

Location

VA Medical Center, Cleveland

Cleveland, Ohio, 44106, United States

Location

VA Pittsburgh Health Care System

Pittsburgh, Pennsylvania, 15240, United States

Location

VA Medical Center, Providence

Providence, Rhode Island, 02908, United States

Location

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, 77030, United States

Location

VA Salt Lake City Health Care System, Salt Lake City

Salt Lake City, Utah, 84148, United States

Location

VA Medical & Regional Office Center, White River

White River Junction, Vermont, 05009-0001, United States

Location

Wlliam S. Middleton Memorial Veterans Hospital, Madison

Madison, Wisconsin, 53705, United States

Location

Zablocki VA Medical Center, Milwaukee

Milwaukee, Wisconsin, 53295-1000, United States

Location

VA Medical Center, San Juan

San Juan, 00921, Puerto Rico

Location

Related Publications (11)

• DePalma RG, Hayes VW, Cafferata HT, Mohammadpour HA, Chow BK, Zacharski LR, Hall MR. Cytokine signatures in atherosclerotic claudicants. J Surg Res. 2003 May 15;111(2):215-21. doi: 10.1016/s0022-4804(03)00075-1.

  PMID: 12850465 RESULT

• DePalma RG, Hayes VW, May PE, Cafferata HT, Mohammadpour HA, Brigg LA, Chow BK, Shamayeva G, Zacharski LR. Statins and biomarkers in claudicants with peripheral arterial disease: cross-sectional study. Vascular. 2006 Jul-Aug;14(4):193-200. doi: 10.2310/6670.2006.00039.

  PMID: 17026909 RESULT

• Zacharski LR, Chow BK, Howes PS, Shamayeva G, Baron JA, Dalman RL, Malenka DJ, Ozaki CK, Lavori PW. Reduction of iron stores and cardiovascular outcomes in patients with peripheral arterial disease: a randomized controlled trial. JAMA. 2007 Feb 14;297(6):603-10. doi: 10.1001/jama.297.6.603.

  PMID: 17299195 RESULT

• DePalma RG, Hayes VW, Zacharski LR. Bloodletting: past and present. J Am Coll Surg. 2007 Jul;205(1):132-44. doi: 10.1016/j.jamcollsurg.2007.01.071. Epub 2007 May 17. No abstract available.

  PMID: 17617342 RESULT

• Depalma RG, Hayes VW, Chow BK, Shamayeva G, May PE, Zacharski LR. Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J Vasc Surg. 2010 Jun;51(6):1498-503. doi: 10.1016/j.jvs.2009.12.068. Epub 2010 Mar 20.

  PMID: 20304584 RESULT

• Depalma RG, Zacharski LR. Iron reduction benefits: positive results from a "negative" prospective randomized controlled trial. Vasc Endovascular Surg. 2012 Oct;46(7):596-7. doi: 10.1177/1538574412456304. Epub 2012 Aug 17. No abstract available.

  PMID: 22903331 RESULT

• Zacharski LR, Shamayeva G, Chow BK. Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease. Am Heart J. 2011 Nov;162(5):949-957.e1. doi: 10.1016/j.ahj.2011.08.013.

  PMID: 22093213 RESULT

• Zacharski LR, Chow BK, Howes PS, Shamayeva G, Baron JA, Dalman RL, Malenka DJ, Ozaki CK, Lavori PW. Decreased cancer risk after iron reduction in patients with peripheral arterial disease: results from a randomized trial. J Natl Cancer Inst. 2008 Jul 16;100(14):996-1002. doi: 10.1093/jnci/djn209. Epub 2008 Jul 8.

  PMID: 18612130 RESULT

• Zacharski LR, Chow BK, Howes PS, Lavori PW, Shamayeva G. Implementation of an iron reduction protocol in patients with peripheral vascular disease: VA cooperative study no. 410: the Iron (Fe) and Atherosclerosis Study (FeAST). Am Heart J. 2004 Sep;148(3):386-92. doi: 10.1016/j.ahj.2004.03.027.

  PMID: 15389223 RESULT

• Zacharski LR, Chow B, Lavori PW, Howes PS, Bell MR, DiTommaso MA, Carnegie NM, Bech F, Amidi M, Muluk S. The iron (Fe) and atherosclerosis study (FeAST): a pilot study of reduction of body iron stores in atherosclerotic peripheral vascular disease. Am Heart J. 2000 Feb;139(2 Pt 1):337-45. doi: 10.1067/mhj.2000.102909.

  PMID: 10650308 RESULT

• DePalma RG, Zacharski LR, Chow BK, Shamayeva G, Hayes VW. Reduction of iron stores and clinical outcomes in peripheral arterial disease: outcome comparisons in smokers and non-smokers. Vascular. 2013 Aug;21(4):233-41. doi: 10.1177/1708538113478776.

  PMID: 23518844 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Intermittent Claudication; Peripheral Vascular Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Arterial Disease; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Zacharski R. Leo

  VA Medical & Regional Office Center, White River

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2002
• First Posted: March 20, 2002
• Study Start: May 1, 1999
• Primary Completion: April 1, 2005
• Study Completion: September 1, 2005
• Last Updated: January 21, 2013

Record last verified: 2013-01

Locations

US (23); PR (1)