Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant
For many patients with blood cancers, stem cell transplantation from a family member or from an unrelated donor remains the only potentially curative option. Unfortunately, up to 40% of patients develop chronic lung disease after the transplant, which substantially increases the risk of death in the long-term. Currently, patients with transplant-related lung disease are treated with some combination of steroids and other immunosuppressant drugs, but only about 1 out of 5 improve.
The importance of our study is that the investigators aim to prevent the development of transplant-related chronic lung disease in the first place. Because a strong risk factor for such chronic lung disease is a prior viral respiratory tract infection, the investigators think there is a window of opportunity to intervene. As soon as "cold and flu" symptoms start, the investigators will treat patients with a combination of drugs aimed at eliminating damaging immune responses triggered by the virus. In the absence of such treatment, the investigators believe these lung-damaging immune responses would persist even after the virus disappears. Our hope is that preventive treatment might avoid the development of chronic lung disease, and this would substantially increase long-term survival in our transplant patients.
This is a pilot study. Once feasibility is established, the investigators will seek to expand this study into a definitive clinical trial.
|Respiratory Tract Infections Bronchiolitis Obliterans Cryptogenic Organizing Pneumonia Lung Diseases, Interstitial||Drug: Prednisone Drug: Azithromycin Drug: Montelukast Drug: Symbicort||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|Official Title:||Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study|
- Cumulative incidence of new chronic lung disease [ Time Frame: 6 months following diagnosis of the viral respiratory tract infection ]The incidence rate of new non-infectious pulmonary complications within the 6 month follow-up period will be calculated. Non-infectious pulmonary complications include new airflow obstruction, new restrictive lung disease, and new mixed obstruction/restriction as measured by spirometry at study enrolment, 2 and 8 weeks following viral infection, and by full pulmonary function tests at 3 and 6 weeks following viral infection.
- Prevalence of non-infectious pulmonary complications [ Time Frame: 6 months following the diagnosis of viral respiratory tract infection ]Non-infectious pulmonary complications (NIPCs) include airflow obstruction, restrictive lung disease, and mixed obstruction/restriction as determined by pulmonary function tests. The prevalence of NIPCs will be determined among subjects surviving to 6 months post viral respiratory tract infection.
- Long-term functional impairment as defined by need for supplemental oxygen [ Time Frame: 6 months post viral respiratory tract infection ]The percentage of subjects needing at least 1 month of supplemental oxygen on most days per week, not counting the period of symptomatic viral respiratory tract infection, will be determined in both arms.
- Patient-perceived long-term functional impairment [ Time Frame: 6 months post viral respiratory tract infection ]A FACT-BMT questionnaire will be administered at baseline and again to subjects surviving 6 months post respiratory tract infection to measure patient-perceived functional impairment.
- Time to clearance of viral infection [ Time Frame: Every 2 weeks until virus is no longer detectable ]Subjects in whom a respiratory virus is detected will undergo repeat testing every 2 weeks until the virus is no longer detectable. This is an exploratory analysis. The natural history of many of these community-acquired viruses in the transplant population is not known.
- Incidence of progression to respiratory failure [ Time Frame: 21 days after enrolment ]This endpoint includes admission to hospital because of documented desaturation, need for supplemental oxygen, and need for mechanical ventilation.
- Incidence of bacterial or fungal superinfection [ Time Frame: Within 21 days after enrolment ]The incidence of secondary bacterial and fungal pneumonias will be compared in the two arms, to verify that the added immunosuppression does not contribute to further infectious complications.
- Incidence of various other infectious complications [ Time Frame: Within 6 months after enrolment ]The incidence of various other infectious complications, specifically including but not limited to CMV reactivations and CMV disease, zoster, and septicemia will be monitored in both arms.
- Overall survival from date of viral respiratory tract infection [ Time Frame: 3 months post enrolment ]
- Overall survival from date of viral respiratory tract infection [ Time Frame: 6 months post enrolment ]
- Overall survival from date of transplant to end of study follow-up [ Time Frame: 6 months post enrolment ]
- Overall survival at 1 year post-transplant [ Time Frame: 1 year post-transplant ]This measure will be applied to the group overall and also analyzed according to subgroups of patients presenting viral respiratory tract infections within 30 days of transplant, 31-100 days of transplant, and 101-365 days of transplant.
- Cumulative incidence of death attributable to transplant associated lung disease [ Time Frame: 6 months post enrolment ]
- Cumulative incidence of death from other causes [ Time Frame: 6 months post enrolment ]
|Study Start Date:||September 2011|
|Study Completion Date:||December 30, 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
No Intervention: Standard of Care
Standard of Care includes fluids, antipyretics, ribavirin for RSV infection, and oseltamivir for influenza infection, and intravenous immune globulin for patients with low IgG levels.
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
Prednisone 0.75 mg/kg actual body weight/day PO for 7 days followed by a 7 day taper.
Other Names:Drug: Azithromycin
Azithromycin 250 mg PO daily for 2 weeks, then 3 times per week until 3 monthsDrug: Montelukast
Montelukast 10 mg PO qhs for 3 months
Other Name: SingulairDrug: Symbicort
Symbicort 200/6 mcg, 2 inhalations every 12 hours for 3 months
Please refer to this study by its ClinicalTrials.gov identifier: NCT01432080
|Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont)|
|Montreal, Quebec, Canada, H1T 2M4|
|Principal Investigator:||Elizabeth F Krakow, MD,CM, FRCPC||Maisonneuve-Rosemont Hospital|
|Principal Investigator:||Sandra Cohen, MD, FRCPC||Maisonneuve-Rosemont Hospital|