Patient population and study design
hypophosphatemia
IRON OVERLOAD, SECONDARY, HYPOPHOSPHATEMIA, SYSTEMIC INFECTION
COVAC-EFFECT is a secondary analysis performed in a subpopulation of the ongoing EFFECT-KTx study (NCT03769441, also covering COVAC-EFFECT), a randomized, placebo-controlled, parallel-arm clinical trial aiming to address the effects of FCM versus placebo on exercise tolerance, cardiac function and other clinical outcomes in iron-deficient KTRs. In the mother trial, 158 subjects receive up to four doses of FCM (containing 500 mg Fe3+ per dose) or placebo (0.9% sodium chloride solution) intravenously, with six-week intervals. In case of severe hypophosphatemia (plasma phosphate ≤1.55 mg/dL) or active systemic infection on the day of the study visit, one treatment is withheld. In case of imminent iron overload, defined as a plasma ferritin level of ≥800 ug/L or 500-799 ug/L in combination with a transferrin saturation (TSAT) of ≥45% on the day of the study visit, patients in the FCM arm receive a dose of placebo instead of FCM. The study protocol of the EFFECT-KTx study and COVAC-EFFECT was approved by the medical ethical committee of the University Medical Center Groningen (METc 2018/482), conducted in accordance with the principles of the Declaration of Helsinki and consistent with the Good Clinical Practice guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. All participants had given their informed consent prior to enrollment in the EFFECT-KTx study as well as to enrollment in COVAC.The current study could be performed since the ongoing EFFECT-KTx trial coincided with the Dutch national SARS-CoV2 vaccination program. Given this setting, a formal Study design. During participation in the EFFECT-KTx study, iron-deficient kidney transplant recipients are being randomized to receive four doses of ferric carboxymaltose (FCM) or placebo with six-week intervals after baseline measurements, including iron status assessment, have been performed. During or after participation in the EFFECT-KTx study, patients received three vaccinations against SARS-CoV-2. Before the first vaccination and four weeks after the successive vaccinations, anti-SARS-CoV-2 IgG titer was measured. Four weeks after the second vaccination, anti-SARS-CoV-2 T-lymphocyte response was assessed.