Efficacy of recombinant human soluble thrombomodulin for the treatment of acute exacerbation of idiopathic pulmonary fibrosis: a single arm, non-randomized prospective clinical trial
| Autor: | Noriaki Okada, Yasuo Suzuki, Sho Hayakawa, Yasuo Matsuzawa, Tamako Irie, Hagino Rikitake |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Exacerbation medicine.drug_class business.industry Anticoagulant Idiopathic pulmonary fibrosis Recombinant human soluble thrombomodulin 030204 cardiovascular system & hematology medicine.disease Clinical trial 03 medical and health sciences Acute exacerbation 0302 clinical medicine 030228 respiratory system Internal medicine Concomitant Post-hoc analysis medicine Respiratory function Original Research Article Intensive care medicine business Survival rate |
| Zdroj: | Multidisciplinary Respiratory Medicine |
| ISSN: | 2049-6958 |
| DOI: | 10.1186/s40248-016-0074-z |
| Popis: | Background: Coagulation abnormalities are involved in the pathogenesis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). The administration of recombinant human soluble thrombomodulin (rhTM), which has both anti-inflammatory and anticoagulant activities, improves outcomes and respiratory function in patients with acute respiratory distress syndrome. Therefore, we conducted a prospective clinical study to examine the effects of rhTM on respiratory function, coagulation markers, and outcomes for patients with AE-IPF. Methods: After registration of the protocol, the patients with AE-IPF who satisfied the study inclusion criteria were treated daily with 380 U/kg of rhTM for 7 days and steroid pulse therapy. The concomitant administration of immunosuppressants and polymyxin B-immobilized fiber column treatment was prohibited. The sample size was 10 subjects. The primary study outcome was the improvement of PaO2/FiO2 ratio a week after treatment initiation. Secondary outcomes were change in D-dimer level over time and 28-day survival rate in patients without intubation. Study data were compared with historical untreated comparison group, including 13 patients with AE-IPF who were treated without rhTM before the registration. Results: The mean PaO2/FiO2 ratio for the rhTM treatment group (n = 10) on day 8 significantly improved compared with that on day one (two-way analysis of variance, p = 0.01). The mean D-dimer level tended to decrease in the rhTM group on day 8, but the change was not significant. The 28-day survival rate was 50 % higher in the rhTM group than in the historical untreated comparison group, but the difference was not significant. A post hoc analysis showed that overall survival time was significantly longer in the treated group compared with that of the historical untreated comparison group (p = 0.04, log-rank test). Conclusion: rhTM plus steroid pulse therapy improves respiratory functions in patients with AE-IPF and is expected to improve overall patient survival without using other combination therapies. Trial registration: The study was registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) in October 2012 (UMIN000009082). |
| Databáze: | OpenAIRE |
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