Sperry JL, Guyette FX, Cotton BA
… +29 more, Luther JF, Utarnachitt RB, Kutcher ME, Daley BJ, Peetz AB, Patel MB, Goodman MD, Claridge JA, Patel N, Harbrecht BG, Hashmi ZG, Zarychanski R, Neal MD, Yazer MH, Martin-Gill C, Vincent LE, Harner AM, Meyer DE, Latimer AJ, Robinson BR, McKnight CL, Hinckley WR, Miller KR, Jansen JO, Martin D, Fox EE, Rosario-Rivera BL, Wisniewski SR, TOWAR Study Group
N Engl J Med
· 2026 Jun · PMID 42150044
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BACKGROUND: Blood transfusion before arrival at a hospital reduces mortality from traumatic hemorrhage and shock. Whether transfusion with whole blood is more beneficial than transfusion with blood components is uncertai...BACKGROUND: Blood transfusion before arrival at a hospital reduces mortality from traumatic hemorrhage and shock. Whether transfusion with whole blood is more beneficial than transfusion with blood components is uncertain, as are the effects of the length of time that blood products are in storage between donation and transfusion. METHODS: In this pragmatic, multicenter, phase 3, cluster-randomized trial, we assigned 44 air medical bases in a 2:1 ratio to the use of up to 2 units of whole blood or as-indicated blood components (plasma, red cells, or both) for prehospital transfusion in trauma patients during 1-month blocks. The primary outcome was death from any cause within 30 days after randomization. An observational substudy assessed outcomes according to the storage age of whole blood. RESULTS: Of 1020 eligible patients transported to hospitals by the air bases, 715 were assigned to receive whole blood and 305 to receive blood components; 695 and 298, respectively, were included in the primary analysis. Mortality at 30 days was 25.9% in the whole-blood group and 20.5% in the component group (adjusted odds ratio, 1.24; 95% confidence interval [CI], 0.87 to 1.76; P = 0.24). No substantial between-group differences in adverse events were observed. In the observational substudy, 30-day mortality was 27.1% among 210 patients who received whole blood with a storage age of 15 to 21 days and 26.4% among 443 patients who received whole blood with a storage age of 1 to 14 days (adjusted odds ratio, 0.99; 95% CI, 0.74 to 1.32). CONCLUSIONS: In injured patients with hemorrhagic shock, the use of whole blood for prehospital transfusion did not result in lower 30-day mortality than the use of blood components. (Funded by the Defense Health Agency Research Technology Portfolio Management, Combat Casualty Portfolio; TOWAR ClinicalTrials.gov number, NCT04684719.).
Nathan SD, Smith P, Deng C
… +20 more, King CS, De Salvo M, Weigt SS, Pandya S, Bandyopadhyay D, Lasky JA, Krishna R, Hambly N, Ramaswamy M, Kebbe J, Ettinger N, Gao J, Rao Y, Breytenbach N, Peterson L, Bell H, Behr J, Cottin V, Flaherty KR, TETON-1 Trial Investigators
N Engl J Med
· 2026 May · PMID 42149993
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BACKGROUND: Two phase 3, randomized trials of inhaled treprostinil for idiopathic pulmonary fibrosis (IPF) were conducted on the basis of preclinical and clinical evidence of an antifibrotic mechanism. TETON-2 was comple...BACKGROUND: Two phase 3, randomized trials of inhaled treprostinil for idiopathic pulmonary fibrosis (IPF) were conducted on the basis of preclinical and clinical evidence of an antifibrotic mechanism. TETON-2 was completed first, and results were published; the results of TETON-1 and of both trials combined are reported here. METHODS: In the double-blind TETON-1 trial, we randomly assigned patients with IPF to receive inhaled treprostinil or placebo (12 breaths four times daily). The primary end point was the change in forced vital capacity (FVC) at week 52. Secondary end points, which were analyzed in a prespecified order to control for multiplicity, were clinical worsening (the first occurrence of death from any cause, hospitalization for a respiratory cause, or a relative decline of ≥10% in the percentage of predicted FVC) and acute exacerbation of IPF (each assessed in a time-to-event analysis), survival, change in percentage of predicted FVC, quality of life, and change in diffusion capacity of the lungs for carbon monoxide at week 52. RESULTS: A total of 598 patients underwent randomization and received at least one dose of treprostinil (299 patients) or placebo (299 patients). Of these, 434 completed the assessments through week 52 (218 in the treprostinil group and 216 in the placebo group). The mean age of the patients was 73.0 years, 77.3% were men, and 77.6% were receiving background antifibrotic therapy; the percentage of predicted FVC at baseline was 74.6%. The median change in FVC at week 52 was -43.3 ml (95% confidence interval [CI], -92.1 to -9.1) with treprostinil and -196.2 ml (95% CI, -227.1 to -155.6) with placebo (difference, 130.1 ml; 95% CI, 82.2 to 178.1; P<0.001). Clinical worsening occurred in 95 patients (31.8%) with treprostinil and in 133 patients (44.5%) with placebo (hazard ratio, 0.67; 95% CI, 0.52 to 0.88; P = 0.003). No significant difference was observed in the time to an IPF exacerbation, and no further inferences regarding secondary end points were made. The most frequent adverse event was cough (reported in 54.8% of the patients in the treprostinil group and 33.1% patients in the placebo group). Discontinuation of treprostinil or placebo occurred in 40.5% and 32.8% of the patients, respectively, with adverse event being the primary reason (20.7% and 14.7%). Efficacy and safety outcomes were similar in analyses of the combined trial data. CONCLUSIONS: In patients with IPF, treatment with inhaled treprostinil led to a smaller decline in FVC and fewer clinical-worsening events than placebo over the course of 52 weeks. (Funded by United Therapeutics; TETON-1 ClinicalTrials.gov number, NCT04708782.).
Denninghoff KR, Casper TC, Zorc JJ
… +12 more, Ruddy RM, Satola S, Wendt WJ, Morris CR, Tavarez MM, Lipshaw MJ, Kwok MY, Nesiama JO, Nelson KA, Webb M, Martinez FD, PECARN AZ-SWED Trial Study Group
N Engl J Med
· 2026 May · PMID 42149992
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BACKGROUND: Wheezing illnesses are a leading cause of hospitalization for preschool-age children and are frequently treated with antibiotics. Observational studies have shown more frequent isolation of three pathogenic b...BACKGROUND: Wheezing illnesses are a leading cause of hospitalization for preschool-age children and are frequently treated with antibiotics. Observational studies have shown more frequent isolation of three pathogenic bacteria (, , and ) from nasopharyngeal samples from children with recurrent episodes of wheezing than from those without such illnesses. METHODS: In this multicenter trial, we randomly assigned patients 18 to 59 months of age who presented to an emergency department with a moderate-to-severe episode of wheezing to receive azithromycin once daily at a dose of 12 mg per kilogram of body weight or matching placebo for 5 days. The primary outcome was the sum of scores on the Asthma Flare-up Diary for Young Children (ADYC) over 5 days. Primary-outcome scores could range from 5 to 35, with higher scores indicating more severe wheezing-related symptoms. Efficacy was assessed separately in patients who tested positive for pathogenic bacteria (the positive cohort) and in those who tested negative (the negative cohort). Secondary outcomes were length of stay in the emergency department, length of hospital stay, and return emergency department visits or hospitalizations within 72 hours. Bacterial clearance and antimicrobial resistance were measured at follow-up visits 1 to 3 weeks after randomization. RESULTS: Among 840 patients who underwent randomization, 521 tested positive for pathogenic bacteria. The trial was stopped for futility by the data and safety monitoring board after a planned interim analysis. ADYC scores did not differ significantly between the azithromycin and placebo groups in either the positive cohort (median, 9.59 [interquartile range, 7.29 to 12.60] vs. 9.72 [interquartile range, 7.66 to 12.17]; P = 0.70) or the negative cohort (median, 9.30 [interquartile range, 6.97 to 11.62] vs. 9.10 [interquartile range, 7.19 to 11.45]; P = 0.69). In the positive cohort, bacterial clearance was 58.7% in the azithromycin group and 11.4% in the placebo group. Secondary outcomes appeared to be similar in the two groups for both cohorts, as did the development of bacterial resistance and the incidence of adverse events. CONCLUSIONS: Azithromycin did not lead to a greater reduction in the severity of wheezing-related symptoms than placebo in preschool-age children who presented to the emergency department with moderate-to-severe acute wheezing. (Funded by the National Heart, Lung, and Blood Institute and others; AZ-SWED ClinicalTrials.gov number, NCT04669288.).