Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-µg doses were randomized to receive BNT162b2 30 µg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 µg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 µg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified.

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy.

Objective To measure pharmacokinetics of hydroxyprogesterone caproate (OHPC) and its major metabolites throughout pregnancy. Study Design Thirty women were prescribed OHPC for recurrent preterm birth prevention. Three cohorts of subjects had blood drawn for 7 consecutive days at one of three times: cohort 1 ( n = 6) after the first dose (weeks 16-20), cohort 2 ( n = 8) between weeks 24 and 28, and cohort 3 ( n = 16) between weeks 32 and 36. We measured serum trough levels after week 1 in cohort 1 or after two consecutive weekly doses in cohorts 2 and 3. In 10 subjects, we estimated OHPC terminal half-life at 28 days after their last dose. Results In cohorts 1, 2, and 3, the areas under curve (ng × h/mL) for OHPC were 571.4 ± 195.2, 1,269.6 ± 285.0, and 1,268.0 ± 511.6, respectively. Maximum OHPC levels (ng/mL) were 5.0 ± 1.5, 12.5 ± 3.9, and 12.3 ± 4.9, respectively. The areas under the curve for mono-hydroxylated metabolites were 208.5 ± 92.4, 157.1 ± 64.6, and 211.2 ± 113.1, and maximum concentrations were 1.9 ± 0.7, 1.5 ± 0.7, and 1.8 ± 1.0, respectively. Di-hydroxylated metabolite levels were significantly lower than mono-hydroxylated metabolites. Estimated terminal half-life of OHPC was 16.3 ± 3.6 days and 19.7 ± 6.2 days for the mono-hydroxylated metabolites. Conclusion After the first injection, OHPC maximum serum level was approximately half steady-state level. Measurable metabolites of unknown activity were detected.

Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial.

OBJECTIVE: The objective of the study was to evaluate the efficacy, safety, and tolerability of intravenous ferric carboxymaltose, compared with oral ferrous sulfate in women with postpartum anemia. STUDY DESIGN: In a multicenter, randomized, controlled study, 291 women less than 10 days after delivery with hemoglobin 10 g/dL or less were randomized to receive ferric carboxymaltose (n = 143) 1000 mg or less intravenously over 15 minutes or less, repeated weekly to a calculated replacement dose (maximum 2500 mg) or ferrous sulfate (n = 148) 325 mg orally thrice daily for 6 weeks. RESULTS: Ferric carboxymaltose-treated subjects were significantly more likely to: (1) achieve a hemoglobin greater than 12 g/dL in a shorter time period with a sustained hemoglobin greater than 12 g/dL at day 42, (2) achieve hemoglobin rise 3 g/dL or greater more quickly, and (3) attain higher serum transferrin saturation and ferritin levels. Drug-related adverse events occurred less frequently with ferric carboxymaltose. CONCLUSION: Intravenous ferric carboxymaltose was safe and well tolerated with an efficacy superior to oral ferrous sulfate in the treatment of postpartum iron deficiency anemia.

Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial.

OBJECTIVE: To estimate efficacy of rapid, large-dose intravenous (IV) administration of ferric carboxymaltose compared with oral iron therapy in anemic postpartum women. METHODS: In a randomized, controlled trial, we assigned anemic women (hemoglobin [Hb] less than or equal to 10 g/dL) within 10 days postpartum to receive either IV ferric carboxymaltose (less than or equal to 1,000 mg over 15 minutes, repeated weekly to achieve a total calculated replacement dose) or ferrous sulfate (FeSO(4)) 325 mg orally thrice daily for 6 weeks. RESULTS: One hundred seventy-four patients received 350 IV doses of ferric carboxymaltose (mean total dose 1,403.1 mg) in 3, 2, or 1 injection (10.9%, 79.3%, or 9.8% of patients, respectively); 178 received FeSO(4). Patients assigned to IV ferric carboxymaltose compared with those assigned to oral iron achieved a Hb rise greater than or equal to 2.0 g/dL earlier (7.0 compared with 14.0 days, P<.001), were more likely to achieve a Hb rise greater than or equal to 3.0 g/dL at any time (86.3% compared with 60.4%, P<.001), and were more likely to achieve a Hb greater than 12.0 g/dL (90.5% compared with 68.6%, P<.001). A similar proportion of patients achieved a Hb rise greater than or equal to 2.0 g/dL (96.4% compared with 94.1%, IV compared with oral, P=.443). There were no serious adverse drug reactions. CONCLUSION: Large-dose IV ferric carboxymaltose administration is a new iron agent that is effective for the treatment of postpartum anemia. When compared with oral ferrous sulfate, IV ferric carboxymaltose is better tolerated, prompts a more rapid Hb response, and corrects anemia more reliably. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00396292 LEVEL OF EVIDENCE: I.