Clinical trial sheds new light on potential risk associated with intravenous iron treatment

DURHAM, N.C., Dec. 6, 2018 /PRNewswire/ -- Results from a new clinical trial may shed new light on hypophosphatemia, a condition caused by a drop in phosphate levels in the blood that has emerged as a common side effect of a widely used intravenous iron treatment for iron deficiency anemia.

Although the first line of treatment for iron deficiency anemia is often oral iron, many patients who experience adverse effects require intravenous iron as an alternative treatment. A recent study led by Myles Wolf, MD, MMSc, of the Duke Clinical Research Institute compared the risk of hypophosphatemia in two intravenous iron treatments – ferric carboxymaltose (Injectafer®), which is currently the most widely used on the market, and ferumoxytol (Feraheme®).

The study's results were published today in the journal JCI Insight.

The FIRM trial was a randomized, double-blind trial that investigated 1,997 patients over a period of five weeks. Roughly half of the patients received a total of 1,500 mg of ferric carboxymaltose, while the other half received 1,020 mg of ferumoxytol. Each group received the first half of their treatment at baseline and the second half one week later. Hypophosphatemia is listed as a common side effect on the label for ferric carboxymaltose, but it has generally been considered a benign and transient condition, Wolf said. However, recent case reports and the results from the FIRM trial suggest otherwise.

"In the trial we saw that patients who were treated with ferric carboxymaltose were more likely than patients who received ferumoxytol to experience severe or extreme hypophosphatemia," said William E. Strauss, MD, executive director of medical affairs at AMAG, the company that manufactures ferumoxytol. "These patients were also more likely to have severe hypophosphatemia that persisted at the end of the five week long study."

The FIRM trial results were as follows, for ferric carboxymaltose and ferumoxytol recipients respectively:

• 50.8 percent versus 0.9 percent had severe hypophosphatemia, defined as phosphate levels less than 2.0 mg/dL.
• 10.0 percent versus 0.0 percent had extreme hypophosphatemia, defined as phosphate levels below 1.3 mg/dL.
• 29.1 percent versus 0.0 percent had persistence of severe hypophosphatemia at the end of the five-week study period.

Wolf said these results suggest hypophosphatemia is not always as transient as once thought. He added that recent case reports have shown instances of persistent hypophosphatemia that led to osteomalacia, bone fractures, and other musculoskeletal disorders. Other literature has found that some patients who take a single dose of ferric carboxymaltose have experienced fatigue and shortness of breath.

Researchers were also able to determine which patient populations were at higher risk because of the large study population. Results showed that both women with abnormal uterine bleeding and black patients were high-risk populations. Because kidney failure is associated with reduced ability to excrete phosphate, patients with healthy kidneys are more likely to develop intravenous iron-induced hypophosphatemia. This phenomenon, Wolf said, is a serious concern.

"This problem is slipping through the cracks in the health care system," Wolf said. "Nephrologists often administer intravenous iron, and they focus on phosphate because they treat people with kidney failure who frequently develop hyperphosphatemia," he said. "But they rarely see hypophosphatemia in response to iron because kidney diseases reduces the risk. In contrast, other practitioners who frequently administer intravenous iron to patients at high risk for hypophosphatemia do not think about phosphate levels, and phosphate levels are not measured in standard lab panels.

"Meanwhile patients feel poorly because of their lower phosphate levels, but it is easy to misattribute their symptoms to the original iron deficiency they are being treated for or the underlying disease that caused iron deficiency. If we don't raise clinicians' awareness of hypophosphatemia, it's going to get missed, and grave consequences can ensue." 

About the Duke Clinical Research Institute
The Duke Clinical Research Institute (DCRI), part of the Duke University School of Medicine, is the largest academic research organization in the world. Its mission is to develop and share knowledge that improves the care of patients through innovative clinical research. The DCRI conducts groundbreaking multinational clinical trials, manages major national patient registries, and performs landmark outcomes research. DCRI research spans multiple disciplines, from pediatrics to geriatrics, primary care to subspecialty medicine, and genomics to proteomics. The DCRI also is home to the Duke Databank for Cardiovascular Diseases, the largest and oldest institutional cardiovascular database in the world, which continues to inform clinical decision-making more than 45 years after its founding.

SOURCE Duke Clinical Research Institute