Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Eliminating catheter-associated urinary tract infections in the intensive care unit: is it an attainable goal?

BACKGROUND: Purpose of this study is to determine strategies to decrease catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients. METHODS: ICU patients with an indwelling urinary catheter (UC) in one tertiary hospital were monitored for CAUTI. Interventions were implemented sequentially with quarterly data collection. Outcome measures were infection ratio (IR = number of infections/catheter days [CD] × 1000) and device utilization rate (DUR = catheter days/patient days). RESULTS: CDs and DUR decreased (fiscal year 2008: CD, 11,414; DUR, .85 vs fiscal year 2013: CD, 8,144; DUR, .70). IR increased with suspension of prepackaged baths (IR, 3.2 to 3.5 to 4.9 to 5.0), twice daily UC care (IR, 4.8 to 6.7), emptying UC bags at 400 mL (IR, 6.7 to 9.2). Two-person UC placement (IR, 5.6 to 4.8), physician notification of CAUTI (IR, 6.1 to 4.8), and reinstitution of prepackaged baths and daily UC care (IR, 4.8 to 3.7) decreased CAUTI rates. CONCLUSIONS: Decreasing CAUTI in the ICU requires diligent monitoring and constant practice re-evaluation. Elimination of CAUTI in the ICU may not be possible.