Table 1

Schedule of study interventions

AssessmentScreening (day 14 to −1)Randomisation (day 0)Dose titration (days 14 and 28)Dose finalisation (day 42)Clinic visit (day 112)Clinic visit (day 224)Wean clinic visit (day 336)Stop clinic visit (day 350)Close-out clinic visit (day 364)
Informed consentX
Medical historyXXXXXXXXX
Concomitant medicationsXXXXXXXXX
Physical examinationXXXXXXXXX
Safety laboratory assessments*X
Questionnaires†XXX
TroponinX
Pro-NT BNP/CRP/fibrinogenXX
Urine pregnancyX
Spirometry‡XXXXX
ECGXXXXXXX
6 min walkXXX
RandomisationX
Drug dispensingXXXXXX
Adverse event assessmentXXXXXXXX
Drug return and accountabilityXXXXXX

  • Phone call days 2, 3, 15, 16, 56, 168, 280, 343, 357, 378 for adverse event assessment.

  • Visit windows ±3 days until dose finalisation visit then ±14 days until Wean visit then ±3 days until close-out visit.

  • Unscheduled visits will include medical history, adverse event assessment, and ECG and spirometry if during titration period until day 42; after day 42, the ECG and spirometry are at PI discretion.

  • *Complete blood count, comprehensive metabolic profile including magnesium and liver function tests.

  • †Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, St George Respiratory Questionnaire, Short Form-36, San Diego Shortness of Breath Questionnaire; Personal HEART Score at screening only.

  • ‡Prebronchodilator and postbronchodilator spirometry at screening, otherwise postbronchodilator only; not done at days 112 and 336 if patient has had an acute exacerbation in the 2 weeks prior.

  • BNP, brain natriuretic peptide; CRP, C reactive protein.