Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents

2017 ◽  
Vol 14 (2) ◽  
pp. e129-e137
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vijay Maruti Patil ◽  
Shripad D. Banavali ◽  
Sudeep Gupta ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Randomized Trial ◽  
Iron Deficiency Anemia ◽  
Oral Iron ◽  
Phase Iii ◽  
Deficiency Anemia ◽  
Erythropoiesis Stimulating Agents ◽  
Patients With Cancer

Treatment of Iron-Deficiency Anemia with IV Ferumoxytol in CKD Patients: Efficacy Compared with Oral Iron across Different Age Groups.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2679-2679 ◽  
Author(s):  
Louis Brenner ◽  
Paul Miller ◽  
Sally Rodriguez ◽  
Nainesh Parikh ◽  
Daniel W. Coyne
Keyword(s):  
Side Effects ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Age Groups ◽  
The Elderly ◽  
Oral Iron ◽  
Phase Iii ◽  
Deficiency Anemia ◽  
Iv Iron ◽  
Iron Replacement

Abstract Iron deficiency anemia is common in the elderly. It is an important medical issue particularly in patients with chronic kidney disease (CKD) because of the associated complications, including increased mortality, loss of functional independence, and cognitive and cardiovascular abnormalities. Oral iron replacement is frequently ineffective, being poorly tolerated due to GI side effects. Ferumoxytol, a novel semi-synthetic carbohydrate-coated iron oxide nanoparticle, is being developed as an IV iron therapy to treat iron deficiency anemia in adults and elderly CKD patients. Ferumoxytol is isotonic with plasma, has lower free iron than other available IV products, and can be given as a 510 mg dose via rapid IV bolus. To evaluate the safety and efficacy of iron replacement with ferumoxytol relative to oral iron in adults and elderly subjects with CKD, data were pooled from three open-label, multicenter, randomized Phase III trials (ClinicalTrials.gov identifiers NCT00255437, NCT00255424, and NCT00233597). In a modified ITT Population (subjects randomized and dosed), a total of 884 subjects with CKD stages 1–5 and 5D received either 2 doses of 510 mg of IV ferumoxytol within 5±3 days or 200 mg of elemental oral iron daily for 21 days (Ferro-Sequels®). The mean change from baseline to Day 35 for hemoglobin (Hgb, the primary endpoint in these Phase III studies) was analyzed using an ANOVA with fixed effects for treatment and age categories (<50, 50 to <65, 65 to <75, and ≥75 years) and their interaction. There was a highly significantly greater Hgb response with IV ferumoxytol relative to oral iron across all age groups (mean ± SD were 1.03±1.22 g/dL for ferumoxytol vs. 0.42±1.05 g/dL for oral iron, p<0.0001). The Hgb response to IV ferumoxytol was consistently observed regardless of age and was greater than the response seen with oral iron (see Table for mean ± SD values). By contrast, there appeared to be a diminished response to oral iron with increasing age. Subject incidences of adverse events with ferumoxytol were similar to or lower than those observed with oral iron in all 3 studies. Multiple factors, including patient compliance, concomitant medications, and impaired GI absorption and/or side effects, may contribute to the ineffectiveness of oral iron. Therefore, physicians should consider the use of IV iron to more effectively treat iron deficiency anemia in all adult CKD patients, including the elderly. Change in Hemoglobin at Day 35 Ferumoxytol 2×510 mg Oral Iron Age N Baseline Hgb Change in Hgb at Day 35 N Baseline Hgb Change in Hgb at Day 35 Relative Change in Hgb (Ferumoxytol vs Oral Iron) All 605 10.15 ± 0.81 1.03 ± 1.22 279 10.33 ± 0.78 0.42 ± 1.05 245% <50 105 10.22 ± 0.96 1.06 ± 1.38 38 10.16 ± 0.96 0.58 ± 1.42 183% 50 to <65 192 10.14 ± 0.80 1.00 ± 1.13 112 10.40 ± 0.79 0.43 ± 1.07 233% 65 to <75 163 10.14 ± 0.76 0.92± 1.19 70 10.33 ± 0.75 0.46 ± 0.89 200% ≥75 145 10.10 ± 0.74 1.17 ± 1.27 59 10.28 ± 0.69 0.25 ± 0.89 468%

Ferumoxytol Treatment Results in Robust Hemoglobin Increases in Iron Deficiency Anemia Patients with a History of Unsatisfactory Oral Iron Therapy in a Phase III, Randomized, Placebo-Controlled Trial.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2098-2098
Author(s):  
Saroj Vadhan Raj ◽  
Michael Cressman ◽  
David Ford ◽  
William Strauss ◽  
Gerri Poss ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Group Treatment ◽  
Oral Iron ◽  
Phase Iii ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Oral Iron Therapy ◽  
History Of ◽  
Iv Iron

Abstract Abstract 2098 Background: Although oral iron therapy is often the initial approach to the treatment of iron deficiency anemia (IDA), many patients fail to adequately respond or do not tolerate oral iron. Unfortunately for these patients, approved treatment options are limited in the US and Canada to only the IV iron dextrans, which have boxed safety warnings and inconvenient dosing regimens. Many of these patients, therefore, do not get IV iron, and remain inadequately treated and symptomatic. Ferumoxytol (FER), a new IV iron approved for the treatment of IDA in patients with chronic kidney disease (CKD), is being investigated to treat IDA patients without CKD who have a history of unsatisfactory oral iron therapy or in whom oral iron cannot be used. This randomized, placebo-controlled, double blind trial was designed to assess the efficacy and safety of FER for the treatment of these IDA patients. Methods: Key inclusion criteria included a Baseline hemoglobin (Hgb) less than 10 g/dL and >7 g/dL, and transferrin saturation (TSAT) <20%. Subjects were randomized 3:1 to receive 2 injections of either FER (510 mg, 5±3 days apart) or placebo (IV normal saline). Efficacy assessments included comparisons of the change in Hgb, TSAT and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the 2 treatment groups between Baseline and Week 5. Results: A total of 808 subjects were randomized to the 2 treatment arms (FER, n=608; placebo, n=200). FER demonstrated superiority to placebo with 81.1% of subjects achieving an increase in Hgb of >2.0 g/dL from Baseline to Week 5 compared to only 5.5% in the placebo group (treatment difference: 75.6%, p<0.0001). At each post-FER treatment time point, a larger percentage of FER-treated subjects had a >2.0 g/dL increase in Hgb compared with those treated with placebo. The superiority of FER was also demonstrated for the mean change in Hgb from Baseline to Week 5 with a robust 2.7 g/dL increase compared to only 0.1 g/dL in the placebo group (treatment difference: 2.54 g/dL, p<0.0001). An increase in TSAT from Baseline to Week 5 was only observed in FER-treated subjects (mean change: FER, 11.0%; placebo −0.1%). In addition, a statistically significant improvement in fatigue from Baseline to Week 5, as measured by the FACIT-Fatigue, was shown for FER-treated subjects compared to placebo (p<0.0001). The rates of adverse events (AEs) and related AEs were higher in the FER group, although no pattern or safety trend was observed to suggest a specific safety signal. The overall rate of serious adverse events (SAEs) was comparable between the 2 treatment groups (FER, 2.6%; placebo, 3.0%), and treatment-related SAEs associated with the class of IV iron products were reported in 4 (0.7%) FER-treated subjects. As expected, protocol-defined AEs of Special Interest (signs/symptoms of hypotension or hypersensitivity associated with IV iron use) were noted at a higher rate in FER-treated subjects (FER, 3.6%; placebo, 1.0%). All cardiovascular AEs were considered unrelated by the investigators. Overall, FER was well tolerated and no new safety signals were identified. Conclusion: In this randomized, placebo-controlled Phase III trial, 2 doses of FER were shown to be highly effective in raising hemoglobin and iron parameters in non-CKD patients with IDA who had a history of unsatisfactory oral iron therapy. FER also significantly reduced fatigue, and was generally well tolerated with no new safety signals being identified. Therefore, FER could provide an important, new treatment option for IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Disclosures: Vadhan Raj: AMAG Pharmaceuticals, Inc.: Research Funding. Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Cressman:AMAG Pharmaceuticals, Inc.: Employment. Strauss:AMAG Pharmaceuticals, Inc.: Employment. Bernard:AMAG Pharmaceuticals, Inc.: Employment. Li:AMAG Pharmaceuticals, Inc.: Employment. Allen:AMAG Pharmaceuticals, Inc.: Employment.

Efficacy and Safety of IV Ferumoxytol (FER) for Iron Deficiency Anemia (IDA) in Patients with Cancer

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1352-1352
Author(s):  
Saroj Vadhan-Raj ◽  
Naomi V. Dahl ◽  
Kristine Bernard ◽  
Zhu Li ◽  
William Strauss
Keyword(s):  
Iron Deficiency ◽  
Cancer Patients ◽  
Iron Deficiency Anemia ◽  
Study Drug ◽  
Oral Iron ◽  
Deficiency Anemia ◽  
Efficacy And Safety ◽  
Employment Equity ◽  
Patients With Cancer ◽  
Equity Ownership

Abstract Background: IDA is common in cancer patients due to blood loss and inflammation. Many do not tolerate oral iron or adequately respond. Two Phase-3 trials investigated the efficacy and safety of IV FER for treatment of IDA in patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. This analysis explored the impact of IV iron treatment on the subgroup of patients with cancer. Methods: Data from patients with cancer were extracted from 2 RCTs (NCT01114139; NCT01114204) in which patients with baseline (BL) Hgb 7-10g/dL, TSAT <20%, were randomized 3:1 to FER (510mg, 2 injections, over 2-8 days) or placebo (PL), and 2:1 to FER or 1g iron sucrose (IS, 200mg, 5 doses over 14 days). Laboratory and safety data were pooled for this analysis. Differences within groups in change from BL Hgb were analyzed with paired t-test, and between groups were explored with ANCOVA adjusted for BL (missing values imputed as 0 change). Results: The ITT population of all 1413 patients who were exposed to study drug included 98 patients with cancer (median age 60.5, 71% female, 65% white, BL TSAT 9.2±9.7%, ferritin 121 ±187ng/mL). Gastrointestinal cancers were most common (42), followed by breast (14), cervix (10), and lung (9). During the studies, 45 patients received chemotherapy, 19 with platinum-based regimens. ESA doses were neither increased >20% nor initiated in any treatment group. Transfusions were received by 3 (23%) of IS and 6 (8%) of FER patients. Treatment with both IV irons was associated with a significant increase in Hgb by end of study (FER 1.8 g/dL, p<0.0001; IS 1.9 g/dL, p=0.002; Figure 1). Figure 1 Figure 1. However, the response with FER occurred earlier, with a significantly greater increase than IS at week 2 (1.1 vs 0.1, p= 0.007) and greater than PL at week 5 (1.8 vs 0.5 g/dL, p=0.02) (LS means). A summary of the frequency and severity of adverse events among the cancer patients subgroup and the full study populations are provided in Table 1. Abstract 1352. Table 1:Adverse Event SummaryCancer Patients SubgroupPooled Overall Study PopulationAdverse Event (AE) Category, Subjects n(%)Ferumoxytol N=75Iron Sucrose N=13Placebo N=10Ferumoxytol N=1014Iron Sucrose N=199Placebo N=200All AEs48 (64.0)6 (46.2)8 (80.0)467 (46.1)88 (44.2)86 (43.0)Related AEs (1)6 (8.0)01 (10.0)147 (14.5)32 (16.1)15 (7.5)Serious AEs7 (9.3)1 (7.7)1 (10.0)33 (3.3)5 (2.5)6 (3.0)Related Serious AEs2 (2.7)006 (0.6)00AEs of Special Interest (2)4 (5.3)1 (7.7)033 (3.3)10 (5.0)2 (1.0)AEs Resulting in Study Discontinuation0006 (0.6)2 (1.0)2 (1.0)Death (3)1 (1.3)01 (10.0)3 (0.3)01 (0.5) (1) Classified by investigator as related to study drug. (2) Protocol defined – including hypotension and hypersensitivity (3) Assessed as unrelated by the Investigator Conclusions: These results indicate that cancer patients with IDA, who had not tolerated or responded to oral iron, responded to both IV FER and IS with a significant increase in Hgb. The response to IV FER appeared earlier. However,given the relatively small N, limited conclusions can be made, and larger studies will be needed to further define the responses. Disclosures Vadhan-Raj: AMAG Pharmaceuticals, Inc.: Research Funding. Off Label Use: Both of the study drugs, ferumoxytol and iron sucrose, are only approved for the treatment of iron deficiency anemia in patients with chronic kidney disease.. Dahl:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Bernard:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Li:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership. Strauss:AMAG Pharmaceuticals, Inc.: Employment, Equity Ownership.

scholarly journals IRON ABSORPTION AND RESPONSE TO ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA ASSOCIATED TO ASYMPTOMATIC GIARDIASIS.

1993 ◽  
Vol 33 (6) ◽  
pp. 661-661
Author(s):  
Helena U Suzuki ◽  
Mauro B Morais ◽  
Jose N Corral ◽  
Ulisses Fagundes-Neto ◽  
Nelson L Machado
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Absorption ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Oral Iron Therapy

The Treatment of Iron-deficiency Anemia—Palatable but Ineffective Iron Medication

PEDIATRICS ◽  
1963 ◽  
Vol 31 (6) ◽  
pp. 1041-1044
Author(s):  
LOUIS K DIAMOND ◽  
J. LAWRENCE NAIMAN ◽  
DONALD M. ALLEN ◽  
FRANK A. OSKI,
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Ferrous Sulfate ◽  
Oral Iron ◽  
Gastrointestinal Absorption ◽  
Deficiency Anemia ◽  
Therapeutic Effects ◽  
Rapid Rise ◽  
Carbohydrate Complex ◽  
Therapeutic Results

Experience with a new oral iron-carbohydrate complex (Jefron) in the treatment of iron-deficiency anemia shows that the therapeutic results are inferior to those obtainable with ferrous sulfate. Many children showed no response after months of treatment with this drug and when subsequently placed on ferrous sulfate therapy showed a rapid rise in hemoglobin to normal levels. Preliminary studies suggest that poor gastrointestinal absorption may be a factor in the inadequate therapeutic effects.

Intravenous versus Oral iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial

2021 ◽  
Author(s):  
Adam K. Lewkowitz ◽  
Molly J. Stout ◽  
Emily Cooke ◽  
Seon C. Deoni ◽  
Viren D'Sa ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Adverse Reactions ◽  
Controlled Trial ◽  
Oral Iron ◽  
Deficiency Anemia ◽  
Randomized Controlled ◽  
Iv Iron ◽  
Severe Adverse Reactions

Objective Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. Study Design This open-label RCT randomized patients with IDA (hemoglobin [hgb] <10 g/dL and ferritin <30 ng/mL) at 24 to 34 weeks' to oral iron or single 1,000-mg dose of IV low-molecular weight iron dextran over one hour. The primary outcome was maternal anemia at delivery (hgb < 11 g/dL). Secondary outcomes were mild/moderate or severe adverse reactions, maternal hgb and ferritin at delivery, blood transfusion, gestational age at delivery, birth weight, neonatal hgb and ferritin, and composite neonatal morbidity. Analysis was as per protocol. Results The trial was stopped early for logistical reasons, and the data analyzed as preliminary data to inform a larger, potentially externally funded, definitive trial. Of 55 patients approached, 38 consented. Of these, 15 were withdrawn: 5 received IV iron from their primary obstetrician after being randomized to oral iron and 10 declined to receive IV iron. Of the remaining 23 patients, who were included in the analytic population, 13 received oral iron and 10 received IV iron. The rate of maternal anemia at delivery (hgb < 11 g/dL) was high overall but significantly reduced with IV iron (40 vs. 85%, p = 0.039). Rates of maternal hgb < 10 g/dL were significantly lower in the IV iron group (10 vs. 54%, p = 0.029). There were no severe adverse reactions and similar rates of mild/moderate reactions between groups. Conclusion IV iron reduces rates of anemia at the time of admission for delivery, supporting a larger RCT comparing IV versus oral iron for the treatment of IDA of pregnancy powered for definitive clinical outcomes. However, issues uncovered in this RCT suggest that patient, clinician, and systems-level barriers associated with different IDA treatment modalities must be considered prior to conducting a larger RCT. This study is registered with clinicaltrials.gov with identifier no.: NCT03438227. Key Points

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