Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00032357
Status:
COMPLETED
Last Update Posted:
2013-01-21
First Post:
2002-03-19
Brief Title:
Does the Reduction of Total Body Iron Storage TBIS Alter Mortality in a Population of Patients With Advanced PVD
Sponsor:
US Department of Veterans Affairs
Organization:
VA Office of Research and Development
Study Overview
Official Title:
CSP 410 - The Iron Fe and Atherosclerosis Study FeAST
Status:
COMPLETED
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FeAST
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 1277 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
Detailed Description:
The original JAMA abstract 2007 reported no overall effect of iron reduction intervention by phlebotomy However pre-planned analyses according to randomization variables at entry including age and ferritin level were described in the JAMA paper showing improved outcomes with iron reduction with younger age by quartile for the secondary endpoint p for interaction 0004 and also suggested a favorable effect in smokers p for interaction 0006 Age analyzed as a continuous variable using the Cox proportional hazards regression model and log relative hazard plots revealed that age interacted nonlinearly with treatment in both primary p004 and secondary p0001 outcomes The Cox model showed improved primary HR 047 95 CI 024-090 p002 and secondary HR 041 95 CI 024-068 p0001 outcomes in youngest age quartile participants age 43 to 61 randomized to iron reduction versus control Thus an interaction between age and level of body iron may have masked beneficial effects of iron reduction in the overall cohort
Detailed analysis of the effect of age and ferritin levels published in the American Heart Journal confirmed that iron reduction significantly improved primary and secondary outcomes in youngest age quartile participants as described above displayed as Kaplan-Meier plots Mean follow-up ferritin levels MFFL declined with increasing entry age in controls Older age p0026 and higher ferritin p0001 at entry predicted poorer compliance with phlebotomy and rising MFFL in iron reduction participants Iron reduction intervention also produced greater ferritin reduction in younger participants Improved outcomes with lower MFFL occurred in iron reduction patients for both primary HR 111 95 CI 101-123 p0028 and secondary HR 110 95 CI 10-120 p0044 outcomes and for the entire cohort primary outcome HR 111 95 CI 101-123 p0037 Improved outcomes occurred with MFFL below versus above the median of the entire cohort means primary outcome HR 148 95 CI 114-192 p0003 secondary outcome HR 122 95 CI 099-150 p0067
Thus lower iron burden predicted improved outcomes overall and was enhanced with iron reduction by phlebotomy Controlling iron burden may improve survival and prevent or delay non-fatal myocardial infarction and stroke These findings warrant confirmation using further studies
A possible effect of iron levels on risk of cancer as well as vascular disease was recognized at trial inception Participants with visceral malignancy within the preceding five years were excluded from this study However information was collected prospectively on the occurrence of new visceral malignancy and cause-specific mortality including death due to cancer As reported in the Journal of the National Cancer Institute a new visceral malignancy was diagnosed during follow-up in 60 control and 38 iron reduction participants a 37 HR 063 95 CI 042 - 095 p 0026 decrease in risk with iron reduction Reduced cancer risk with iron reduction was confirmed on time-to-event analysis HR 065 95 CI 043 - 097 p 0036 Reduced risk was observed for several common tumor types Iron reduction participants had lower cancer - specific mortality and lower all-cause mortality in participants diagnosed with cancer HR 039 95 CI 021 - 072 p 0003 and HR 049 95 CI 029 - 083 p 0009 respectively compared to control participants MFFL during follow-up in those participants randomized to iron reduction who developed cancer were comparable to levels in control participants t93 08 p 0428 The MFFL in participants randomized to iron reduction developing cancer was 127 ngmL 95 CI 712 - 1830 The MFFL was significantly lower in participants not developing cancer 764 ngmL 95 CI 714 - 814 p 0017 Participants randomized to iron reduction developing cancer appeared to be relatively non-compliant with intervention
Analysis of data from the FeAST study continues to delineate interactions between iron status and smoking lipid levels and statin use diabetes and race It has been shown that ferritin levels ranging from about 70 to 79 ngmL are associated with lower mortality and levels of inflammatory markers Statin use while not a randomization variable has been monitored and shown to relate to lower ferritin levels
Detailed analysis of the effect of age and ferritin levels published in the American Heart Journal confirmed that iron reduction significantly improved primary and secondary outcomes in youngest age quartile participants as described above displayed as Kaplan-Meier plots Mean follow-up ferritin levels MFFL declined with increasing entry age in controls Older age p0026 and higher ferritin p0001 at entry predicted poorer compliance with phlebotomy and rising MFFL in iron reduction participants Iron reduction intervention also produced greater ferritin reduction in younger participants Improved outcomes with lower MFFL occurred in iron reduction patients for both primary HR 111 95 CI 101-123 p0028 and secondary HR 110 95 CI 10-120 p0044 outcomes and for the entire cohort primary outcome HR 111 95 CI 101-123 p0037 Improved outcomes occurred with MFFL below versus above the median of the entire cohort means primary outcome HR 148 95 CI 114-192 p0003 secondary outcome HR 122 95 CI 099-150 p0067
Thus lower iron burden predicted improved outcomes overall and was enhanced with iron reduction by phlebotomy Controlling iron burden may improve survival and prevent or delay non-fatal myocardial infarction and stroke These findings warrant confirmation using further studies
A possible effect of iron levels on risk of cancer as well as vascular disease was recognized at trial inception Participants with visceral malignancy within the preceding five years were excluded from this study However information was collected prospectively on the occurrence of new visceral malignancy and cause-specific mortality including death due to cancer As reported in the Journal of the National Cancer Institute a new visceral malignancy was diagnosed during follow-up in 60 control and 38 iron reduction participants a 37 HR 063 95 CI 042 - 095 p 0026 decrease in risk with iron reduction Reduced cancer risk with iron reduction was confirmed on time-to-event analysis HR 065 95 CI 043 - 097 p 0036 Reduced risk was observed for several common tumor types Iron reduction participants had lower cancer - specific mortality and lower all-cause mortality in participants diagnosed with cancer HR 039 95 CI 021 - 072 p 0003 and HR 049 95 CI 029 - 083 p 0009 respectively compared to control participants MFFL during follow-up in those participants randomized to iron reduction who developed cancer were comparable to levels in control participants t93 08 p 0428 The MFFL in participants randomized to iron reduction developing cancer was 127 ngmL 95 CI 712 - 1830 The MFFL was significantly lower in participants not developing cancer 764 ngmL 95 CI 714 - 814 p 0017 Participants randomized to iron reduction developing cancer appeared to be relatively non-compliant with intervention
Analysis of data from the FeAST study continues to delineate interactions between iron status and smoking lipid levels and statin use diabetes and race It has been shown that ferritin levels ranging from about 70 to 79 ngmL are associated with lower mortality and levels of inflammatory markers Statin use while not a randomization variable has been monitored and shown to relate to lower ferritin levels
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None