Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant | RxWiki

Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Respiratory Tract Infections Bronchiolitis Obliterans Cryptogenic Organizing Pneumonia Lung Diseases, Interstitial
Intervention	Drug: Prednisone Drug: Azithromycin Drug: Montelukast Drug: Symbicort
Phase	Phase 2
Sponsor	Maisonneuve-Rosemont Hospital
Responsible Party	Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier	NCT01432080
First Received	September 8, 2011
Last Updated	January 8, 2012
Last verified	January 2012

Tracking Information[ + expand ][ + ]

First Received Date	September 8, 2011
Last Updated Date	January 8, 2012
Start Date	September 2011
Estimated Primary Completion Date	Not Provided
Current Primary Outcome Measures	Cumulative incidence of new chronic lung disease [Time Frame: 6 months following diagnosis of the viral respiratory tract infection] [Designated as safety issue: No]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.
Current Secondary Outcome Measures	Prevalence of non-infectious pulmonary complications [Time Frame: 6 months following the diagnosis of viral respiratory tract infection] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: Yes]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] [Designated as safety issue: Yes]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] [Designated as safety issue: Yes]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] [Designated as safety issue: No] Overall survival from date of viral respiratory tract infection [Time Frame: 6 months post enrolment] [Designated as safety issue: No] Overall survival from date of transplant to end of study follow-up [Time Frame: 6 months post enrolment] [Designated as safety issue: No] Overall survival at 1 year post-transplant [Time Frame: 1 year post-transplant] [Designated as safety issue: No]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] [Designated as safety issue: No] Cumulative incidence of death from other causes [Time Frame: 6 months post enrolment] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief Title	Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant
Official Title	Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Condition	Respiratory Tract Infections Bronchiolitis Obliterans Cryptogenic Organizing Pneumonia Lung Diseases, Interstitial
Intervention	Drug: Prednisone Prednisone 0.75 mg/kg actual body weight/day PO for 7 days followed by a 7 day taper. Other Names: Deltasone Steroids Drug: Azithromycin Azithromycin 250 mg PO daily for 2 weeks, then 3 times per week until 3 months Drug: Montelukast Montelukast 10 mg PO qhs for 3 months Other Names: SingulairDrug: Symbicort Symbicort 200/6 mcg, 2 inhalations every 12 hours for 3 months Other Names: Budesonide Formoterol
Study Arm (s)	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. Experimental: SAMS Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	70
Estimated Completion Date	Not Provided
Estimated Primary Completion Date	December 2012
Eligibility Criteria	Inclusion Criteria: - Allogeneic transplant within the prior 1 year - Age greater than or equal to 18 years - Capable of informed consent - Neutrophil engraftment has occurred - This is the first clinically-recognized episode of viral respiratory tract infection after transplant Exclusion Criteria: - Proof or high suspicion for bacterial, fungal or any non-viral microorganism causing pneumonia - CMV, VZV or HSV pneumonia - Prior diagnosis of a chronic transplant-related non-infectious pulmonary complication (ex: BO, COP) - Treating physician believes the risk of systemic steroids is too great - Currently receiving prednisone at or greater than 0.25 mg/kg/day or the equivalent dose of another steroid - Currently receiving pentostatin - Mycophenolate initiated de novo or increased within the past 4 weeks - Use of inhaled corticosteroids within the past 2 weeks for at least 1 week - Haploidentical or T-cell depleted graft - Lack of pre-transplant pulmonary function tests - Evidence of a prior symptomatic viral respiratory tract infection following transplant, whether treated or not - Allergy or adverse reaction to any of the study drugs - Relapse or progression of the underlying malignancy - Palliative care
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Johanne Blais (514) 252-3400 johanne_blais.hmr@ssss.gouv.qc.ca
Location Countries	Canada

Administrative Information[ + expand ][ + ]

NCT Number	NCT01432080
Other Study ID Numbers	HMR1102
Has Data Monitoring Committee	No
Information Provided By	Maisonneuve-Rosemont Hospital
Study Sponsor	Maisonneuve-Rosemont Hospital
Collaborators	The Canadian Blood and Marrow Transplant Group
Investigators	Principal Investigator: Elizabeth F Krakow, MD,CM, FRCPC Maisonneuve-Rosemont HospitalPrincipal Investigator: Sandra Cohen, MD, FRCPC Maisonneuve-Rosemont Hospital
Verification Date	January 2012

Locations[ + expand ][ + ]

Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont)	Montreal, Quebec, Canada, H1T 2M4 Contact: Johanne Blais \| (514) 252-34003295 \| johanne_blais.hmr@ssss.gouv.qc.ca Principal Investigator: Elizabeth F Krakow, MD,CM, FRCPC Recruiting