D. S. Riley, Letter to the Editor: Chronic kidney disease, anemia, and epoetin, N Engl J Med, 2007. 356(9): p. 956.
This is a letter to the editor of the New England Journal of Medicine pointing out the potential benefits of Proferrin® brand HIP. It mentions the thought that free-radical-induced oxidative stress from IV iron may be responsible for tissue damage in patients with chronic kidney disease. However, there is a potential reduction in oxidative stress as well as a cost savings associated with Proferrin® brand HIP use.
A. R. Nissenson, et al., Clinical evaluation of heme iron polypeptide: sustaining a response to rHuEPO in hemodialysis patients. Am J Kidney Dis, 2003. 42(2): p. 325-330.
Proferrin® brand HIP was used to determine if the use of HIP alone in Hemodialysis (HD) patients could sustain the response to rHuEPO in these patients during a 6-month period. Stable HD patients on renal replacement therapy for a minimum of 6 months were selected. And only those patients who were administered maintenance IV iron infusions and rHuEPO were selected. In total, 37 patients were selected for this study and 28 patients completed the study. Three months of baseline data was collected to confirm that hematocrit (Hct), serum ferritin, and transferring saturation (TSAT) values were within Dialysis Outcomes Quality Initiatives (DOQI) recommended parameters, which at the time were TSAT greater than 20% and ferritin level greater than 100 ng/mL. Patients either continued treatment with their respective clinic’s IV iron protocol or were administered HIP at 21 mg/d (low dose) or 36 mg/d (high dose) of elemental iron. Data was collected monthly including a monthly questionnaire to assess GI side effects.
During the study period, Proferrin® brand HIP successfully replaced IV iron therapy in the majority of HD patients and maintained target Hct with no concomitant use of IV iron. This treatment was associated with a significant increase in EPO efficiency. Three subjects (8%) discontinued the study due to GI side effects (primarily flatulence and bloating) reported with Proferrin® brand HIP use.
S. Ghaddar and G. M. Moore, Abstract: Evaluation of the ability of heme iron polypeptide to sustain response to rHuEPO in peritoneal dialysis patients: A prospective clinical evaluation. NKF Presentation, April 7, 2003, Dallas, Texas.
Proferrin® brand HIP was studied to determine if HIP could be a successful alternative to other iron therapy in peritoneal dialysis (PD) patients. Twelve stable PD patients were selected and administered Proferrin® brand HIP. Baseline data was collected for 3 months which included Hct and serum iron levels as well as monthly rHuEPO dose and monthly IV iron dose. At time zero, patients were instructed to discontinue all non-heme iron supplementation and consume 24 mg elemental iron as Proferrin® brand HIP. The therapy continued for 4 months and data was collected every month. A questionnaire was also given to assess side effects.
There were no significant changes observed in Hct or serum iron levels. The serum iron levels increased slightly and the average rHuEPO monthly dose decreased slightly over the 4 month period. Proferrin® brand HIP was able to sustain response to rHuEPO in PD patients without concomitant IV iron use. The total elemental iron dose from Proferrin® brand HIP was significantly lower (p = 0.0001) than the mean total iron dose from ionic iron during the baseline period. There was also a reported reduction in GI side effects (flatulence) with Proferrin® brand HIP use.
Nagaraju S.P., Cohn A., Akbari A., Davis J.L., Zimmerman D.L. Heme iron polypeptide for the treatment of iron deficiency anemia in non-dialysis chronic kidney disease patients: A randomized controlled trial. BMC Nephrol. 2013;14 doi: 10.1186/1471-2369-14-64
Proferrin® brand HIP was studied to determine if HIP was as effective as IV iron sucrose as a treatment of iron-deficiency anemia for patients with non-dialysis chronic kidney disease (ND-CKD). Baseline data was collected for 6 months for 18 patients in the HIP group and 22 patients in the IV sucrose group. Hemoglobin concentration [Hb], % transferrin saturation (TSAT), ferritin levels, and adverse events were reported and compared. Over a 6 month period, TSAT and Hb concentrations increased in both the HIP and IV sucrose groups at similar rates. Serum ferritin was significantly higher in the IV iron sucrose group; however it is unclear if these greater values are clinically significant. Four patients in each group had an adverse event with gastrointestinal complaints being the most common. Symptomatic hypotension occurred in three patients in the IV iron sucrose group during infusion.
Abdelazim IA, Abu-Faza M, Elbiaa AA, Othman HS, Alsharif DA, Elsawah WF. Heme iron polypeptide (proferrin®-ES) versus iron saccharate complex (ferrosac) for treatment of iron deficiency anemia during pregnancy. Acta Med Int 2017;4:56-61
This study compared the efficacy and safety of Heme Iron Polypeptide (Proferrin ES) versus iron sachharate complex in treatment of iron deficiency anemia during pregnancy. A total of 250 patients were selected based on low hemoglobin levels due to iron deficiency anemia. The 3 month post treatment hemoglobin levels, ferritin levels, and mean corpuscular volume (MCV) increased in both groups. 3 month post treatment reticulocytes count decreased in both study groups, with no significant difference. Only 1.6% (2/124) of studied patients reported gastrointestinal intolerance to oral Proferrin ES. It was concluded that both HIP (Proferrin ES) and intravenous iron sachharate complex were efficacious for treatment of iron deficiency during pregnancy, increasing hemoglobin levels and replacing depleted iron storage.
Varsha Narayanan, Amit Bhargava. In Clinic Effectiveness of Heme Iron Polypeptide in Women with Iron Deficiency Anemia Nonresponsive or Noncompliant to Conventional Iron Supplements. J Gynecol Women’s Health. 2018: 11(5): 555822. DOI: 10.19080/JGWH.2018.11.555822
In this study, 270 women diagnosed with iron deficiency anemia, visiting gynecology clinics and who were on conventional iron supplements, with poor gastrointestinal tolerance and compliance were evaluated for their Hemoglobin (Hb) and Serum Ferritin, and then treated with daily tablets of Heme Iron polypeptide (HIP) and followed up within a month for reassessment. Hemoglobin and Serum Ferritin assessed at start of HIP therapy (baseline) were repeated at the next follow up visit along with recording patients’ tolerability to therapy.
The rise in Hb was highly significant at the follow up visit in women who had baseline Hb indicating moderate and severe anemia (moderate group Hb rise in non-pregnant, pregnant: 1.15g/dl, 1.48g/dl and severe group Hb rise in non-pregnant, pregnant: 1.56g/dl, 2.75g/dl; P< 0.001). There was also a significant decline in the number of patients with severe anemia, as well as those with low ferritin. The adverse event related discontinuation rate was1% indicating a satisfactory tolerance and compliance to treatment.
Conclusion: This real-world study suggests that oral HIP therapy can be an effective treatment option in pregnant and non-pregnant women with Iron deficiency anemia due to gastrointestinal tolerability, compliance and efficacy in improving hematological parameters.
Narayanan, Varsha & Bhargava, Amit. (2018). Real-World Efficacy and Tolerability of Heme Iron Polypeptide in Non-Pregnant and Pregnant Women with Iron Deficiency Anemia. International Journal of Medical Research and Health Sciences. 7.
378 non-pregnant and pregnant women visiting 56 gynecology clinics across India with an in-clinic diagnosis of iron deficiency anemia based on baseline laboratory evaluation of hemoglobin (Hb), along with ferritin, MCV and hematocrit, were treated with daily tablets of heme iron polypeptide (HIP) for an average duration of 3 months. Laboratory parameters assessed at baseline were repeated at final follow up and the patients’ tolerability to therapy was also recorded.
Results: In non-pregnant women, the average rise in Hb was 1.17, 2.06 and 3.28 (g/dl), in groups with baseline mild, moderate, and severe anemia, while in pregnant women, the average Hb rise was 2.70 and 3.53 (g/dl) in groups with baseline moderate and severe anemia. The rise in Hb was highly significant in both pregnant and non-pregnant women with baseline moderate and severe anemia. There was also a significant decline in the number of patients with moderate and severe anemia, as well as in percentage patients with low ferritin, MCV and hematocrit values. The tolerability of HIP was satisfactory with a treatment adverse event related discontinuation rate of less than 0.8%.
Conclusion: This study suggests that oral HIP therapy can be an effective treatment option in pregnant and non-pregnant women with iron deficiency due to its better gastrointestinal tolerability and efficacy in improving hematological parameters.
P. A. Seligman, G. M. Moore, and R. B. Schleicher, Clinical studies of HIP: an oral heme-iron product. Nutrition Research, 2000. 20(9): p. 1279-1286.
Iron absorption studies were performed to evaluate HIP. Absorption of HIP was compared to iron salts and placebo. In the study, 14 subjects were given a standard breakfast and tested with three different preparations: 20 mg of iron as HIP; 20 mg of iron as ferrous fumarate and placebo. Change in serum iron was measured at 3 hours and 6 hours post ingestion. Statistical analysis was done using paired T tests. HIP allowed for significantly increased iron absorption taken with a meal when compared to iron salts or placebo (p<0.03 and p<0.02, respectively).
There was a correlation between iron stores, as estimated by serum ferritin, and iron absorption from HIP with iron absorption from HIP significantly increased compared to placebo for those with lower ferritin values. Thus, HIP is bioavailable when taken with a meal and would have potential advantages over iron salts as a supplement.