Background
The study hypothesis is that administration of inhaled NO plus oxygen to subjects with submassive pulmonary embolism (PE) will improve RV systolic function; reduce RV strain and necrosis while improving patient dyspnea more than treatment with oxygen alone.
Methods
This paper describes the rationale and protocol for a registered (NCT01939301), a nearly completed Phase II, three-center, randomized, double blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 h) with blood sampling before and after treatment, and mandatory echocardiography and high sensitivity troponin post treatment to assess the composite primary endpoint. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=0.05 and β=0.20. Safety was ensured by continuous spectrophotometric monitoring of %methemoglobinemia, and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software and physical shielding of the device display and query of the clinical care team to assess blinding efficacy.
Results
We have enrolled 78 patients over a 31 month period. No patient has been withdrawn stopped as a result of a safety concern, and no patient has had a serious adverse event related to NO.
Conclusions
We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE.
Objective: To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE.Methods: This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had
In this sample of children and teenagers with suspected PE, the PERC rule was negative in 31%, and demonstrated good overall diagnostic accuracy, including a low false negative rate. These data support the need for a large, prospective diagnostic validation study of PERC in children.
D-dimer is currently ordered in children for suspected PE in the emergency care setting, mostly in teenagers. The observed lower limit 95% CIs of 89% and 54% for diagnostic sensitivity and the specificity, respectively, suggest if used in patients with low-clinical probability, a normal D-dimer can safely exclude PE in children.
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