June 7, 2016 First ever hard endpoint trial with IV iron (Monofer®) in chronic heart failure

First ever hard endpoint randomised controlled trial looking at effect of intravenous iron, Monofer® (iron isomaltoside), in chronic heart failure about to start

The "Effectiveness of Intravenous iron treatment vs standard care in patients with heart failure and iron deficiency: a randomised, open-label multicentre trial (IRONMAN)'' has been approved by UK Ethics Committee and the Medicines & Healthcare Products Regulatory Authority (MHRA) and is now ready to include patients. The study will be the largest and longest running study conducted in patients with iron deficiency and CHF due to left ventricular (LV) systolic dysfunction. A total of 1,300 patients will be enrolled in the study via multiple sites across the UK. This makes IRONMAN not only the largest randomised controlled trial of IV iron in CHF but the largest trial ever made comparing IV iron to a comparator that is not IV iron. Patients will be randomised to either Monofer® or standard therapy not allowing for IV iron.

Several studies1-8 with different IV iron preparations have shown a consistent picture of symptom improvement in iron deficient CHF patients in response to IV iron treatment independently of whether the patients were anaemic or not. However, so far no studies have been powered to evaluate the impact on 'hard endpoints' such as cardiovascular death or hospitalisation - demonstrating a beneficial impact on such endpoints is fundamental to changing standard clinical practice.

IRONMAN has been designed specifically to evaluate the impact of IV iron on hard points (cardiovascular death and recurrent heart failure hospitalisation) in patients with CHF. It will in due course inform evidence based guidelines, directed towards improving quality of life and prognosis of one of the best evaluated diseases in clinical medicine.9 "This is a landmark study that will change clinical practice by determining the role for IV iron in CHF. If positive, the study will help improve the prognosis for patients with heart failure and demonstrate the potential for IV iron to impact outcomes independently of haemoglobin", said Chief Investigator Dr Paul Kalra, Consultant Cardiologist, Portsmouth Hospitals NHS Trust and Honorary Senior Lecturer, University of Glasgow.

The study is sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde and funded through a special project grant from the British Heart Foundation and an unrestricted grant from Pharmacosmos. "We are very proud to support this study. As an iron specialist company, our fundamental objective is to improve outcomes for patients with iron deficiency. This study is a major milestone that may establish Monofer® as a new standard treatment to improve patient outcomes in CHF", said Claes Strom, VP Medical Affairs and Marketing, at Pharmacosmos.

About Monofer

Monofer® is an iron-carbohydrate complex for intravenous administration. Monofer® is already marketed in more than 30 countries, primarily in Europe, for the treatment of iron deficiency and iron deficiency anaemia. Monofer® is under development in the rest of the world, including North America and Japan. Monofer® is manufactured by Pharmacosmos, Denmark.

About iron deficiency

Iron deficiency is a debilitating condition that affects almost 2 billion people worldwide. Iron deficiency is often associated with many chronic diseases such as renal diseases (including Chronic Kidney Disease), cancers (including chemotherapy induced anaemia), gynaecologic disorders (including abnormal uterine bleeding) and gastrointestinal diseases (including inflammatory bowel disease).

About Chronic Heart Failure

Chronic heart failure, a condition where the heart muscle does not pump effectively, affects around 1-2% of the adult population in developed countries, rising to ≥10% among those aged over 70 years. As a consequence of the condition, patients often have impaired quality of life and are unable to carry out routine everyday tasks. There are many different causes of heart failure; the commonest is ischaemic heart disease.

At the age of 55 years, the lifetime risk of developing heart failure is around 1 in 3 for men (33%) and just under 3 in 10 (28%) for women. Improvements in treatments over the last 20-30 years have been associated with improved prognosis in patients with heart failure secondary to left ventricular systolic dysfunction. Yet patients with heart failure frequently suffer from acute exacerbations requiring prolonged hospitalisation and it is associated with an on-going risk of premature death. Recent European data have shown that 12-month all-cause mortality rates for hospitalized and stable/ambulatory HF patients were 17% and 7%, respectively; 12-month hospitalization rates were around 30-40%10.

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  2. Hildebrandt PR, Bruun NE, Nielsen OW, Pantev E, Shiva F, Videbæk L et al. TATM 2010; 11(4):131-137.
  3. Gaber R, Kotb NA, Ghazy M, Nagy HM, Salama M, Elhendy A. Echocardiography 2012; 29(1):13-18.
  4. Usmanov RI, Zueva EB, Silverberg DS, Shaked M. J Nephrol 2008; 21(2):236-242.
  5. Anker SD, Comin CJ, Filippatos G, Willenheimer R, Dickstein K, Drexler H et al. N Engl J Med 2009; 361(25):2436-2448.
  6. Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V et al. Eur Heart J 2014 Aug 31.
  7. Bolger AP, Bartlett FR, Penston HS, O'Leary J, Pollock N, Kaprielian R et al. J Am Coll Cardiol 2006; 48(6):1225-1227.
  8. Toblli JE, Lombrana A, Duarte P, Di GF. J Am Coll Cardiol 2007; 50(17):1657-1665.
  9. McMurray JJ, et al. Eur Heart J 2012;33:1787-847
  10. Ponikowski P et at. DOI: http://dx.doi.org/10.1093/eurheartj/ehw128
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About Pharmacosmos

Headquartered in Denmark, Pharmacosmos is a family-owned, international healthcare company with more than 50 years of innovation and leadership in iron- and carbohydrate-based treatments and solutions for human and animal use.

A research-based company, its ongoing R&D programme focuses on improving the lives of patients with iron deficiency with or without anaemia. More than 1 billion people live with iron deficiency anaemia and it is the leading cause of death for an estimated 180,000 people every year. This makes it one of the largest global health challenges of our time.

Pharmacosmos has subsidiaries in the Nordics, the UK and the US and its products are marketed in more than 80 countries across the world. Its manufacturing facilities are approved, among others, by the Danish Medicines Agency and the US FDA.