Effects of IV Iron Replacement on Exercise Capacity in Individuals With Heart Failure

Heart Failure Clinical Trial

Official title:

Effects of IV Iron Replacement on Exercise Capacity in Individuals With Heart Failure With Reduced Ejection Fraction and Iron Deficiency

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05816265
• Other study ID #: STUDY00001297
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: January 24, 2024
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with heart failure with reduced ejection fraction and iron deficiency will be randomized to either receive iron infusion or be in the control group. The study is looking at how iron replacement affects exercise capacity as measured by peak oxygen uptake.

Description:

Currently 5.7 million people in the United States (US) have Heart Failure and it is expected that by 2030 more than 8 million people will have this condition, accounting for a 46 % increase in prevalence. Iron deficiency and anemia are both common findings in patients with heart failure and contribute to morbidity and mortality. The average cost of hospital admissions for heart failure are about $17,000-25,000; creating a large burden on health-care resources and iron replacement may serve to reduce readmissions at less than a tenth of the cost.

The working hypothesis to support Iron supplementation is that it improves oxygen carrying capacity, thereby improving exercise tolerance. Exercise tolerance in patients with heart failure is an important prognostic indicator.

Role of iron supplementation has been investigated to improve quality of life and outcomes in patients with heart failure and two large multi-centric trails. FAIR-HF and CONFIRM-HF have both showed significant improvement in symptoms and six-minute walk distances in patients with HFrEF after IV iron supplementation. This was found to be true for both anemic and non-anemic patients. Despite the current data, IV iron supplementation is currently only a class IIb recommendation for HFrEF and routine testing of iron studies, is not a part of practice guidelines for heart failure management.

Part of what makes the existing data less compelling is that exercise tolerance was assessed using a 6-minute walk test and though it correlates with functional capacity, it is a sub-maximal exercise test and cannot assess the peak oxygen uptake. Individuals with heart failure are often unable to attain this peak oxygen uptake. The inability to increase O2 uptake with exercise is what affects exercise capacity.

The study aims to bridge the gap between the response seen after IV iron supplementation and the change in physiology we attribute to it using a formal Cardiopulmonary exercise testing. A peak VO2 provides the most objective assessment of functional capacity in patients with HF. This parameter is a surrogate marker for the maximal cardiac output that an individual can achieve. A modest increase in peak VO2 of 6% at 3 months of exercise training has been associated with a reduction in mortality by 5 %.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 40
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age 18-90 years

• New York Heart Association Class II-III heart failure

• Left ventricular dysfunction with left ventricular ejection fraction = 40%

• Ferritin < 100 ng/mL or 100-300 ng/mL with transferrin saturation (TSAT) < 20%

• Patients deemed by an attending physician to require intravenous iron therapy

• The patient is willing and able to comply with the protocol and has provided written informed consent

Exclusion Criteria:

• Iron overload disorders or allergy, concomitant nutritional deficiencies- B12 and folate

• Recent Acute Coronary Syndrome

• Physical barriers to exercise capacity

• Currently presenting in heart failure exacerbation

• Declined participation

• Chronic liver disease

• NYHA class IV

• Active bleeding

• Pregnancy

• Life expectancy = 12 months

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Heart Failure
• Iron-deficiency

Intervention

Drug:
• IV Iron Infusion Group
Subjects will receive IV Iron Infusion. Dosage of iron will be at discretion of physicians

Locations

Country	Name	City	State
United States	Banner - University Medical Center, Phoenix campus	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Radha Gopalan	American Regent, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (11)

Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Luscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P; FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009 Dec 17;361(25):2436-48. doi: 10.1056/NEJMoa0908355. Epub 2009 Nov 17. — View Citation

Ebner N, von Haehling S. Iron deficiency in heart failure: a practical guide. Nutrients. 2013 Sep 23;5(9):3730-9. doi: 10.3390/nu5093730. — View Citation

Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003 Jan 21;107(2):223-5. doi: 10.1161/01.cir.0000052622.51963.fc. — View Citation

Fang J, Mensah GA, Croft JB, Keenan NL. Heart failure-related hospitalization in the U.S., 1979 to 2004. J Am Coll Cardiol. 2008 Aug 5;52(6):428-34. doi: 10.1016/j.jacc.2008.03.061. — View Citation

Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010 Aug;31(15):1872-80. doi: 10.1093/eurheartj/ehq158. Epub 2010 Jun 21. Erratum In: Eur Heart J. 2011 May;32(9):1054. — View Citation

Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J. 2013 Apr;165(4):575-582.e3. doi: 10.1016/j.ahj.2013.01.017. Epub 2013 Feb 22. — View Citation

Lim EA, Sohn HS, Lee H, Choi SE. Cost-utility of ferric carboxymaltose (Ferinject(R)) for iron-deficiency anemia patients with chronic heart failure in South Korea. Cost Eff Resour Alloc. 2014 Sep 10;12:19. doi: 10.1186/1478-7547-12-19. eCollection 2014. — View Citation

Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011 Sep 13;58(12):1241-51. doi: 10.1016/j.jacc.2011.04.040. — View Citation

Swank AM, Horton J, Fleg JL, Fonarow GC, Keteyian S, Goldberg L, Wolfel G, Handberg EM, Bensimhon D, Illiou MC, Vest M, Ewald G, Blackburn G, Leifer E, Cooper L, Kraus WE; HF-ACTION Investigators. Modest increase in peak VO2 is related to better clinical outcomes in chronic heart failure patients: results from heart failure and a controlled trial to investigate outcomes of exercise training. Circ Heart Fail. 2012 Sep 1;5(5):579-85. doi: 10.1161/CIRCHEARTFAILURE.111.965186. Epub 2012 Jul 6. — View Citation

von Haehling S, Ebner N, Evertz R, Ponikowski P, Anker SD. Iron Deficiency in Heart Failure: An Overview. JACC Heart Fail. 2019 Jan;7(1):36-46. doi: 10.1016/j.jchf.2018.07.015. Epub 2018 Dec 12. — View Citation

Wang G, Zhang Z, Ayala C, Wall HK, Fang J. Costs of heart failure-related hospitalizations in patients aged 18 to 64 years. Am J Manag Care. 2010 Oct;16(10):769-76. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exercise Capacity	Cardiopulmonary exercise testing will be administered to measure Peak V02. During the exercise testing a special mouthpiece that can measure oxygen and carbon dioxide is used to measure peak oxygen uptake.	2 months after IV iron infusion
Primary	Patient subjective outcome measures	Subjects will complete the Kansas City Cardiomyopathy Questionnaire.The lowest score is 0 and the highest score is 100. The higher the score is, the better the quality of life.	2 months after IV iron infusion
Secondary	Objective Quality of Life measures	A 6-minute walk test will be administered to determine if the NYHA class has improved.	2 months after IV iron infusion