IV Ferric Carboxymaltose vs Oral Ferrous Sulfate on Physical Performance, QoL, and Cognition in Frail Elderly with Iron Deficiency and CVD: Randomized Controlled Trial

Primary objective: to evaluate the effect of intravenous ferric carboxymaltose versus oral ferrous sulfate and placebo on physical performance, measured by the Short Physical Performance Battery, in frail, iron‑deficient elderly patients with cardiovascular disease over a 12‑month period, addressing a key determinant of functional independence and prognosis. Secondary objectives: – to assess impact on health‑related quality of life using the EQ-5D-5L questionnaire; – to determine the effect on risk of falls during the treatment period; – to evaluate influence on total duration of hospitalizations within the 12‑month follow‑up.

The trial enrolled community-dwelling adults aged 65 years and older, inclusive of both female and male participants, who had a documented diagnosis of cardiovascular disease (e.g., hypertension, atrial fibrillation, heart failure, coronary artery disease, cerebrovascular disease, or peripheral artery disease). Eligibility required a state of frailty defined by a Tilburg Frailty Indicator score of ≥5 points, reduced physical performance of ≤9 points on the Short Physical Performance Battery, and laboratory evidence of iron deficiency (transferrin saturation <20 %). All subjects provided written informed consent and were capable of complying with the study protocol and completing assessments independently. No specific dietary or physical‑activity requirements were imposed for enrollment. The sponsor did not provide information on the total number of participants enrolled.

The trial is a randomized, double-blind, three‑parallel‑group, placebo‑controlled superiority study evaluating intravenous ferric carboxymaltose, oral ferrous sulfate, and matched placebos in elderly participants (≥65 years) with cardiovascular disease, frailty and iron deficiency. After an eligibility screening visit, participants meeting inclusion criteria undergo baseline assessments, receive the first assigned treatment (20 ml infusion of ferric carboxymaltose or 0.9 % sodium chloride and a 247.25 mg oral tablet of ferrous sulfate or oral placebo), and are randomized in a 1:1:1 ratio. Subsequent study visits are scheduled at months 3, 6, 9 and 12 to monitor safety, record the number of falls and hospital days, and repeat the primary outcome measure, the Short Physical Performance Battery, as well as the EQ‑5D‑5L questionnaire. The final visit at month 12 serves as the end‑of‑study assessment. Participant involvement therefore spans approximately 12 months from randomization. Early discontinuation may occur if a participant experiences a serious adverse event, withdraws consent, fails to adhere to the treatment regimen, or develops a condition that, in the investigator’s judgment, precludes continued participation.

The investigational product is ferric carboxymaltose supplied as a dispersion for injection/infusion (Ferinject 50 mg iron/ml). Each dose consists of 20 ml of the solution, delivering 1,000 mg elemental iron, administered intravenously as a single infusion. The infusion is performed under clinical supervision at the study site according to the protocol‑defined schedule and recorded in the infusion log to ensure compliance.

The intravenous placebo consists of 0.9 % sodium chloride solution (Braun), formulated as a solution for infusion. Participants assigned to this arm receive 20 ml of the saline solution by the same infusion procedure and schedule as the active intravenous group, providing blinding of the administration route.

The oral comparator is Tardyferon, a prolonged‑release tablet containing 80 mg of dried ferrous sulfate (equivalent to 247.25 mg of elemental iron). One tablet is taken orally once daily throughout the 12‑month treatment period. Tablet intake is documented in a medication diary and verified by pill count at each study visit.

The oral placebo comprises inert coated tablets matching the appearance of the ferrous sulfate tablets. Participants ingest one tablet daily for the duration of the study. Compliance is monitored through the same diary and pill‑count procedures employed for the active oral arm.

Efficacy will be evaluated by comparing the change from baseline to month 12 in the Short Physical Performance Battery (SPPB) scores among participants receiving intravenous ferric carboxymaltose, oral ferrous sulfate, or placebo. SPPB assessments will be performed at the initial screening visit (baseline) and at the end of the 12‑month treatment period using the standardized protocol for the test.

Secondary efficacy measures include the change in health‑related quality of life as assessed by the EQ‑5D‑5L questionnaire between baseline and month 12, the total number of falls recorded during the 12‑month period, and the total number of days spent in hospital within the same timeframe. The EQ‑5D‑5L will be administered at baseline and month 12 as a patient‑reported outcome instrument. Fall events and hospitalisations will be captured prospectively through participant diaries and verification against medical records. Differences between treatment arms for each endpoint will be calculated to determine the relative effect of the interventions.