Study treatment
Nebulised UFH was administered through a vibrating mesh nebuliser
(NebZmart, Glenmark, Taiwan) with 1.25 ml of the sodium heparin (5,000
IU / 0.25 mL) being diluted with 4 ml of 0.9% saline at 6 hourly
intervals in addition to standard of care, with other patients
randomised to receive only standard of care as the control arm of the
study. Randomisation was 1:1 without any adjustment for any clinical
characteristics. Randomisation was produced by using a computerized
random list generator.
The UFH used was formulated as ampules containing 5,000 IU/0.25 mL, from
Cristalia Ltda, meeting all the requirements of the USP and Brazilian
Pharmacopeia (BP). The heparin samples were analyzed by 1D1H-NMR spectroscopy, gel permeation and anion exchange
chromatographies and had their anticoagulant potencies determined with
anti-FIIa and anti-FXa activity assays, as required by both the USP and
BP. The molecular mass distribution parameters of the formulations also
met the requirement of USP. Besides certified as being from porcine
origin, the formulations showed no contamination with heparins from
other animal sources, as recommended by the BP. The 1D1H-NMR spectrum show no signal at 7.4 ppm, assuring
the absence of benzyl alcohol commonly added as a preservative in
multiuse vials for intravenous administration but not into formulations
intended for subcutaneous use. Furthermore, the formulations used showed
no contamination with oversulfated chondroitin sulfate after analyses by
NMR and anion exchange chromatography.