Ferric carboxymaltose with or without erythropoietin in anemic patients with hip fracture: a randomized clinical trial.

BACKGROUND: The increasing incidence of osteoporotic hip fracture (HF) has raised the requirements of red blood cell (RBC) transfusions, whereas this scarce resource may cause morbidity and mortality. STUDY DESIGN AND METHODS: This study was a multicenter, randomized, double-blind, clinical trial that aimed to assess efficacy of ferric carboxymaltose (FCM) with or without erythropoietin (EPO) in reducing RBC transfusion in the perioperative period of HF. Participants (patients > 65 years admitted with HF and hemoglobin [Hb] levels of 90-120 g/L) were randomly assigned to receive a preoperative single dose of 1 g of FCM (short intravenous [IV] infusion over 15 min), plus 40,000 IU of subcutaneous EPO (EPOFE arm); versus 1 g of IV FCM plus subcutaneous placebo (FE arm); and versus IV and subcutaneous placebo (placebo arm). Primary endpoint was the percentage of patients who received RBC transfusion, and secondary endpoints were the number of RBC transfusions per patient, survival, hemoglobinemia, and health-related quality of life (HRQoL; by means of Short Form 36 Version 2 questionnaire). RESULTS: A total of 306 patients (85% women, mean age 83 ± 6.5 years) were included. A total of 52, 51.5, and 54% of patients required RBC transfusion in the EPOFE, FE, and placebo arms, respectively, with no significant differences in the number of RBC transfusions per patient, survival, HRQoL, and adverse events among treatment groups. A significant increase in Hb levels was achieved at discharge (102 g/L vs. 97 g/L) and 60 days after discharge (125 g/L vs. 119 g/L) in the EPOFE arm with respect to placebo arm; in addition, a higher rate of patients recovered from anemia in the EPOFE arm with respect to the placebo arm (52% vs. 39%), 60 days after discharge. CONCLUSION: Preoperative treatment with FCM alone or in combination with EPO improved recovery from postoperative anemia, but did not reduce the needs of RBC transfusion in patients with HF.

Ferric carboxymaltose with or without erythropoietin for the prevention of red-cell transfusions in the perioperative period of osteoporotic hip fractures: a randomized contolled trial. The PAHFRAC-01 project.

BACKGROUND: Around one third to one half of patients with hip fractures require red-cell pack transfusion. The increasing incidence of hip fracture has also raised the need for this scarce resource. Additionally, red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality. This makes it necessary to develop blood-saving strategies. Our objective was to assess safety, efficacy, and cost-effictveness of combined treatment of i.v. ferric carboxymaltose and erythropoietin (EPOFE arm) versus i.v. ferric carboxymaltose (FE arm) versus a placebo (PLACEBO arm) in reducing the percentage of patients who receive blood transfusions, as well as mortality in the perioperative period of hip fracture intervention. METHODS/DESIGN: Multicentric, phase III, randomized, controlled, double blinded, parallel groups clinical trial. Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate. Patients will be treated with either a single dosage of i.v. ferric carboxymaltose of 1 g and subcutaneous erythropoietin (40.000 IU), or i.v. ferric carboxymaltose and subcutaneous placebo, or i.v. placebo and subcutaneous placebo. Follow-up will be performed until 60 days after discharge, assessing transfusion needs, morbidity, mortality, safety, costs, and health-related quality of life. Intention to treat, as well as per protocol, and incremental cost-effectiveness analysis will be performed. The number of recruited patients per arm is set at 102, a total of 306 patients. DISCUSSION: We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture. CLINICALTRIALS.GOV IDENTIFIER: NCT01154491.

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study.

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period.

A single-dose, open-label, parallel, randomized, dose-proportionality study of paliperidone after intramuscular injections of paliperidone palmitate in the deltoid or gluteal muscle in patients with schizophrenia.

Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotic, developed for monthly intramuscular (i.m.) administration into deltoid/gluteal muscle, approved for the treatment of schizophrenia in many countries. To assess the options for i.m. injection sites, dose-proportionality of PP was investigated after injection of a single dose (25-150 mg eq.) of PP in either gluteal (n = 106) or deltoid (n = 95) muscle of schizophrenic patients. Overall, mean (geometric) area under plasma concentration-time curve from time zero to infinity (AUC∞ ) of paliperidone increased proportionally with increasing PP doses, regardless of injection site. Mean maximum plasma concentration (Cmax ) was slightly less than dose-proportional for both injection sites at PP doses >50 mg eq. Mean Cmax was higher after injection in the deltoid compared with the gluteal muscle, except for the 100 mg eq. dose, while AUC∞ for both injection sites was comparable at all doses. Median time to reach Cmax (tmax ) ranged from 13-14 days after deltoid and 13-17 days after gluteal injection across all doses. Single PP injections in deltoid and gluteal muscles in the dose range of 25-150 mg eq. were generally tolerable both locally and systemically.