Table 1.
Summary of RCT Studies
| Study | Treatment Evaluated | Population | Treatment Arm Sample Size | Mean Dose per Patient (g) | Study Duration (Weeks) | Hypophosphatemia Rate (%) | Definition of Hypophosphatemia | Serum Phosphate Measurement Methodology |
|---|---|---|---|---|---|---|---|---|
| Onken et al9,a | FCM | IDA refractory to oral iron (poor toleration or response to oral iron) | 489 | 1.435 | 5 | 4.6% | Not defined, likely serum phosphate < 2.0 mg/dL | Not explicitly reported |
| Van Wyck et al16,b | FCM | Women with IDA and history of heavy uterine bleeding | 228 | 1.568 | 6 | 68.9% | Serum phosphate < 2.0 mg/dL | Phosphate appears to be measured at baseline, week 1, 2, 4, and 6 |
| Qunibi et al23,c | FCM | IDA patients with NDDCKD | 147 | 1.218 | 8 | 2.7% | Not defined | Lab tests at baseline, weeks 2, 4, 6 and 8 or early termination visit |
| Charytan et al24 | FCM | IDA patients 18–85 with CKD | 204 | 1 (exact dose not specified) | 4 | 4.3% | Not defined | Lab and safety data collected “before and after study drug administration” |
| Bailie et al25,d | FCM | IDA of any etiology & intolerance/unsatisfactory response to oral iron | 559 | 0.962 | 2 | 16.0% | Not defined | Phosphate appears to be measured at weeks 1 & 2 |
| Onken et al (REPAIR-IDA)26,e | FCM | IDA patients with non-dialysis-dependent CKD | 1276 | 1.5 (exact dose not specified) | 8 | 18.5% | Not defined | Serum phosphate measured at “multiple study visits” for “development of potentially clinically significant changes in serum phosphate” |
| Iron Sucrose | 1285 | 1(exact dose not specified) | 0.8% | |||||
| Hussain et al39,f | FCM | IDA of any etiology & intolerance/unsatisfactory response to oral iron | 82 | 1.45 | 6 | 8.5% | Serum phosphate < 2.0 mg/dL | Clinical evaluation of phosphate at baseline, week 1, 2, 4, 6 |
| Iron Dextran | 5 | 1.34 | 0.0% | |||||
| Barish et al44,g | FCM | IDA of any etiology & intolerance/unsatisfactory response to oral iron | 343 | 0.75 | 5 | 7.3% | Serum phosphate < 2.0 mg/dL | Labs measured on days 0, 7 and 30 or end-of-treatment visit for single-dose study and days 0, 7, 14, 28, and 42 or end-of-study for multidose study |
| Seid et al27,h | FCM | Women with postpartum IDA or IDA due to heavy uterine bleeding | 996 | 0.944 | 5 | 0.6% | Not defined, likely serum phosphate < 2.0 mg/dL | Lab values determined from blood samples obtained at days 0 and 30 |
| Wolf et al40,i | FCM | Women with IDA and history of heavy uterine bleeding | 17 | 0.91 | 5 | 58.8% | Serum phosphate < 2.0 mg/dL | Labs at baseline, days 1, 7, 14, and 35. If phosphate was below normal range after day 0, patients had testing at 14 day intervals until return to normal reference range |
| Jose et al28 | FCM | Pregnancy-related IDA | 50 | 1.7396 ± 0.1055 | 12 | 4.0% | Not defined | Phosphate likely measured at baseline, week 3, 6, 12 |
| Iron Sucrose | 50 | 1.7304 ± 0.1219 | 6.0% | |||||
| Ikuta et al29,j | FCM | Digestive disease-related IDA | 39 | 1.1836 ± 0.340 | 12 | 92.1% | Phosphate below 2.5 mg/dL at least once during study | General labs at weeks 1, 2, 4, 6, 8, and 12 |
| Ikuta et al45,k | FCM | Women with AUB IDA | 119 | 0.9882 or 1.4582 (dependent on dose assignment) | 12 | 18.5% | Not defined, described only as “phosphorus decreased” | General labs at baseline and weeks 1, 2, 4, 6, 8, and 12 |
| Adkinson et al (FIRM)41,l | FCM | IDA refractory to oral iron(any etiology besides dialysis dependent CKD) | 992 | 1.458 | 5 | 38.7% | Serum phosphate <2.0 mg/dL at 2 weeks, (CTCAE grade 3 “severe”) | Phosphate and fractional excretion of phosphate evaluated at baseline, week 2, and week 5 |
| Ferumoxytol | 994 | 0.994 | 0.4% | |||||
| Derman et al30,m | Iron Sucrose | IDA of various etiology | 168 | 1.128 | 5 | 0.0% | Not defined | Serum phosphate measured as a secondary safety endpoint; however timing not reported |
| Breymann et al (FER-ASAP)31,n | FCM | Pregnancy-related IDA | 123 | 1-1.5 (exact dose not specified) | 12 | 8.1% | Not defined | General labs at baseline, weeks 3, 6, 9, and 12 and/or prior to delivery |
| Mahey et al32 | FCM | AUB IDA | 30 | 1.524 ± 0.261 | 12 | 50.0% | Not defined | General labs at baseline, weeks 2, 4, 6, 12 |
| Iron Sucrose | 30 | 1.463 ± 0.196 | 40.0% | |||||
| Macdougall et al (FIND-CKD)33,o | FCM | CKD IDA | 154 | 2.685 | 52 | 0.0% | Not defined | Appendix Figure S4 shows change in serum phosphate from baseline at weeks 4, 8, 12, 24, 36, & 52 |
| Evstatiev etal (FERGICOR)34,p | FCM | IBD IDA | 244 | 1.377 ± 0.381 | 12 | 2.5% | Not defined | General labs at weeks 1, 2, 4, 8, and 12 |
| Iron Sucrose | 239 | 1.160 ± 0.316 | 0.0% |
Notes: aPotentially clinically significant low phosphorus in 53.1% of Group A and 40.7% of Group C. bLowest value of phosphate recorded was 0.9 mg/dL on Day 21 after IV FCM in patient whose baseline phosphate was 2.6 mg/dL. cLowest serum phosphorus level during the study was 1.7 mg/dL. dInvestigators made a judgment as to the clinical significance of any laboratory abnormality to decide lab AEs. eProportion of subjects with potentially clinically significant decreases in phosphate was higher in FCM group compared to iron sucrose group. fAnalysis only considered the 5 patients on LMW iron dextran for iron dextran subgroup. In the FCM group, “the mean [phosphate] value reached its nadir (2.05 mg/dL) at Day 14 and was within the normal range (2.5–4.5 mg/dL) by Day 42”. gOnly reported hypophosphatemia rates within multi-dose subgroup; a significant decrease in phosphorus levels (< 2 mg/dL) was observed in both FCM groups. hPostpartum IDA and HUB groups were combined for analysis. 21.3% of subjects with heavy menstrual bleeding in the FCM group had a transient decrease in serum phosphorus compared to only 0.7% of subjects with postpartum anemia. iIn FCM group, phosphate decreased significantly by 0.6 mg/dL by day 7, and by 0.7 mg/dL by day 14 with recovery by day 35. Among 6 participants whose phosphate remained below normal range at day 35, levels normalized by day 80. jMean serum phosphorus levels reached their lowest values at week 2, and the mean value (± SD) was 1.57 ± 0.48 mg/dL. Phosphorus levels gradually increased after week 4, and the mean level (±SD) recovered to 2.86 ± 0.67 mg/dL at week 12. k65% of subjects in the FCM group had serum phosphate values below the lower limit of normal at week 1, and at week 4, 9.3% of subjects had values < 1.0 mg/dL. One subject in the FCM group had a value <1.0 mg/dL at week 12, achieving recovery on Day 138. lAmong those who received FCM, the mean baseline serum phosphate decreased by 40% by week 2. mThis study reported a 0% hypophosphatemia rate among adverse drug reactions. nPhosphate levels below 2.0 mg/dL (CTCAE severe hypophosphatemia) were recorded in 10 patients; however no hypophosphatemia was reported as TEAEs. oNo data presented on number or percentage of patients with hypophosphatemia; however, mean decrease in serum phosphate was ~0.175mmol/L at 4 weeks and remained ~0.15 mmol/dL or ~0.5mg/dL decreased from baseline at 8 weeks. pOnly reported hypophosphatemia if considered an AE. Mean serum phosphate levels in the FCM group decreased from baseline (1.12 ± 0.22 mmol/L) to week 2 (0.69 ± 0.24 mmol/L) and returned to normal between week 4 and week 12 (1.11 ± 0.23 mmol/L).
Abbreviations: NDDCKD, non-dialysis-dependent chronic kidney disease; CKD, chronic kidney disease; AUB, abnormal uterine bleeding; HUB, heavy uterine bleeding; IBD, inflammatory bowel disease.