Comparison of hemoglobin and transfusion end points by serum hepcidin subgroup and treatment assignment
| . | DA + placebo . | DA + oral iron . | DA + IV iron (pts receiving <4 doses IV iron) . | DA + IV iron (pts receiving 4 or 5 doses IV iron) . | P for comparison of 4 or 5 dose IV iron group with non-IV iron groups . | P for comparison of 4 or 5 dose IV iron group with all other groups . | P for comparison of any IV iron (including <4 doses) with non-IV iron groups . |
|---|---|---|---|---|---|---|---|
| Proportion of patients who achieved a protocol-defined hemoglobin response | |||||||
| Total | 106/163 (65%) | 109/163 (67%) | 40/71 (56%) | 74/92 (80%) | .0079 | .0028 | .23 |
| Hepcidin 1st tertile (≤20.2 ng/mL) | 30/47 (64%) | 26/41 (63%) | 12/20 (60%) | 24/26 (92%) | .0050 | .0038 | .083 |
| Hepcidin 2nd tertile (>20.2-64.3 ng/mL) | 36/53 (68%) | 32/53 (60%) | 6/11 (55%) | 20/21 (95%) | .0048 | .0018 | .069 |
| Hepcidin 3rd tertile (>64.3 ng/mL) | 23/36 (64%) | 29/37 (78%) | 14/24 (58%) | 25/36 (69%) | .99 | .88 | .44 |
| Hepcidin missing | 17/27 (63%) | 22/32 (69%) | 8/16 (50%) | 5/9 (56%) | .68 | .54 | .22 |
| Proportion of patients who required RBC transfusion | |||||||
| Total | 22/163 (13%) | 21/163 (13%) | 12/71 (17%) | 8/92 (9%) | .25 | .12 | .79 |
| Hepcidin 1st tertile | 6/47 (13%) | 4/41 (10%) | 2/20 (10%) | 0/26 (0%) | .072 | .073 | .18 |
| Hepcidin 2nd tertile | 8/53 (15%) | 9/53 (17%) | 2/11 (18%) | 0/21 (0%) | .049 | .047 | .16 |
| Hepcidin 3rd tertile | 6/36 (17%) | 5/37 (14%) | 4/24 (17%) | 6/35 (17%) | .78 | .82 | .77 |
| Hepcidin missing | 2/27 (7%) | 3/32 (9%) | 4/16 (25%) | 2/9 (22%) | .21 | .39 | .054 |
| . | DA + placebo . | DA + oral iron . | DA + IV iron (pts receiving <4 doses IV iron) . | DA + IV iron (pts receiving 4 or 5 doses IV iron) . | P for comparison of 4 or 5 dose IV iron group with non-IV iron groups . | P for comparison of 4 or 5 dose IV iron group with all other groups . | P for comparison of any IV iron (including <4 doses) with non-IV iron groups . |
|---|---|---|---|---|---|---|---|
| Proportion of patients who achieved a protocol-defined hemoglobin response | |||||||
| Total | 106/163 (65%) | 109/163 (67%) | 40/71 (56%) | 74/92 (80%) | .0079 | .0028 | .23 |
| Hepcidin 1st tertile (≤20.2 ng/mL) | 30/47 (64%) | 26/41 (63%) | 12/20 (60%) | 24/26 (92%) | .0050 | .0038 | .083 |
| Hepcidin 2nd tertile (>20.2-64.3 ng/mL) | 36/53 (68%) | 32/53 (60%) | 6/11 (55%) | 20/21 (95%) | .0048 | .0018 | .069 |
| Hepcidin 3rd tertile (>64.3 ng/mL) | 23/36 (64%) | 29/37 (78%) | 14/24 (58%) | 25/36 (69%) | .99 | .88 | .44 |
| Hepcidin missing | 17/27 (63%) | 22/32 (69%) | 8/16 (50%) | 5/9 (56%) | .68 | .54 | .22 |
| Proportion of patients who required RBC transfusion | |||||||
| Total | 22/163 (13%) | 21/163 (13%) | 12/71 (17%) | 8/92 (9%) | .25 | .12 | .79 |
| Hepcidin 1st tertile | 6/47 (13%) | 4/41 (10%) | 2/20 (10%) | 0/26 (0%) | .072 | .073 | .18 |
| Hepcidin 2nd tertile | 8/53 (15%) | 9/53 (17%) | 2/11 (18%) | 0/21 (0%) | .049 | .047 | .16 |
| Hepcidin 3rd tertile | 6/36 (17%) | 5/37 (14%) | 4/24 (17%) | 6/35 (17%) | .78 | .82 | .77 |
| Hepcidin missing | 2/27 (7%) | 3/32 (9%) | 4/16 (25%) | 2/9 (22%) | .21 | .39 | .054 |
Comparison of hemoglobin response and RBC transfusion needs in the MC04CC trial, stratified by serum hepcidin level. MC04CC trial eligibility included hemoglobin <11.0 g/dL, serum ferritin >20 ng/mL, and transferrin saturation <60%.8 Median transferrin saturation of enrolled patients was 18.5% and median ferritin was 324 ng/mL. The study’s primary end point was a hemoglobin increment of ≥2.0 g/dL in the absence of transfusions or achievement of hemoglobin of ≥12.0 g/dL; transfusion avoidance was a secondary end point. There was no overall erythropoietic benefit from parenteral iron compared with oral iron or placebo. All P values are for 2-sided χ2 test, comparing within tertile/row.
DA, darbepoetin alfa; pts, patients; RBC, red blood cells.