| Methods |
Open‐label, randomized, controlled, multicenter, prospective trial Study length: 12 weeks |
| Participants |
Eligibility: Hb ≤ 11 g/dL; serum ferritin ≥ 100 ng/ml; TSAT between 15% and 35%; ECOG PS: 0 to 2; received no epoetin alfa or IV iron within 30 days and no oral iron within 7 days before enrollment; age ≥ 18 years old; life expectancy ≥ 24 weeks Sex (number enrolled): female (89), male (40) Experimental arm: ESAs + oral ferrous sulfate: enrolled 61, analyzed 44 Control arm: ESAs only: enrolled 63, analyzed 44 |
| Interventions |
Experimental arm: ESAs + oral ferrous sulfate 325 mg 3 daily Control arm: ESAs only: epoetin alfa 40,000 U SC once weekly |
| Outcomes |
|
| Notes |
Hematopoietic response defined as increase in Hb level of ≥ 2 g/dL. Patients were excluded for hemolysis, gastrointestinal bleeding, folate or vitamin B12 deficiency, elevated serum ferritin (900 ng/ml) or TSAT (35%), pregnancy or lactation,liver dysfunction (grade 2 based on National Cancer Institute Common Toxicity Criteria), renal dysfunction (serum creatinine 2.0 mg/dl), active infection requiring systemic antibiotics, personal or family history of hemochromatosis, comorbidities precluding study participation, hypersensitivity to sodium ferric gluconate complex or its components, contraindication to epoetin alfa therapy, RBC transfusion within the past 2 weeks, or any investigational agent within 30 days before enrollment. For epoetin alfa treatment: if after 4 weeks Hb did not increase by ≥ 1 g/dl, the dose was increased to 60,000 U once weekly. If Hb increased > 1.3 g/dl in any 2‐week period, the dose was reduced by 25%. If Hb increased to > 13 g/dl, epoetin alfa was discontinued until Hb decreased to ≤ 12 g/dl, and was then resumed at 75% of the previous dose. Grading for treatment‐related harms was not reported. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
High risk |
Study described as “randomized controlled,” but this information is insufficient to permit judgment about the sequence generation process as it lacks details of how sequence was generated |
| Allocation concealment (selection bias) |
Low risk |
“randomization was conducted centrally to avoid selection bias” |
| Blinding (performance bias and detection bias)
All outcomes |
High risk |
There was no blinding (study described as “open‐label”), yet outcome measurement was likely to be influenced by lack of blinding |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Trial authors reported that “except for number of transfusions and patients receiving transfusions,” analysis of primary and secondary efficacy endpoints was based on “evaluable population,” that is performed per protocol. In addition, the imputation method used, that is “last observed data recorded for each parameter before receiving a transfusion were carried forward through the endpoint,” could potentially bias the results |
| Selective reporting (reporting bias) |
Low risk |
Benefits and harms were reported as indicated in a prespecified method |
| Other bias |
Low risk |
Prespecified values of sample size, alpha, beta (power), and delta were provided |
