title: Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial.
abstract: We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. Secondary end-points included haemodynamic changes and 6-min walk distance (6MWD). Overall, 104 adverse events were reported, of which 25 were serious; eight of the latter were considered drug-related. After 12 weeks of therapy, mean cardiac output increased (4.4 ± 1.5 L · min(-1) to 5.5 ± 1.8 L · min(-1)), pulmonary vascular resistance (PVR) decreased (648 ± 207 dyn · s(-1) · cm(-5) to 528 ± 181 dyn · s(-1) · cm(-5)) and mean pulmonary artery pressure (mPAP) remained unchanged compared with baseline. Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased. The 6MWD increased from 325 ± 96 m at baseline to 351 ± 111 m after 12 weeks. Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: Michael
authors.initials: M
authors.lastname: Halank
authors.forename: Heinrike
authors.initials: H
authors.lastname: Wilkens
authors.forename: Andreas
authors.initials: A
authors.lastname: Günther
authors.forename: Gerrit
authors.initials: G
authors.lastname: Weimann
authors.forename: Irmingard
authors.initials: I
authors.lastname: Gebert
authors.forename: Hanno H
authors.initials: HH
authors.lastname: Leuchte
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behr
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006162:Guanylate Cyclase / Q000097:blood / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D017563:Lung Diseases, Interstitial / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism; D010865:Pilot Projects; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D016896:Treatment Outcome
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat; D010100:Oxygen