Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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). |
Drug: Prednisone
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 months
Drug: Montelukast
Montelukast 10 mg PO qhs for 3 months
Other Names:
Drug: Symbicort
Symbicort 200/6 mcg, 2 inhalations every 12 hours for 3 months
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cumulative incidence of new chronic lung disease [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.
Secondary Outcome Measures
- Prevalence of non-infectious pulmonary complications [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 [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 [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 [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 [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 [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 [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 [3 months post enrolment]
- Overall survival from date of viral respiratory tract infection [6 months post enrolment]
- Overall survival from date of transplant to end of study follow-up [6 months post enrolment]
- Overall survival at 1 year post-transplant [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 [6 months post enrolment]
- Cumulative incidence of death from other causes [6 months post enrolment]
Eligibility Criteria
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:
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Proof or high suspicion for bacterial, fungal or any non-viral microorganism causing pneumonia
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CMV, VZV or HSV pneumonia
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Prior diagnosis of a chronic transplant-related non-infectious pulmonary complication (ex: BO, COP)
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Treating physician believes the risk of systemic steroids is too great
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Currently receiving prednisone at or greater than 0.25 mg/kg/day or the equivalent dose of another steroid
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Currently receiving pentostatin
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Mycophenolate initiated de novo or increased within the past 4 weeks
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Use of inhaled corticosteroids within the past 2 weeks for at least 1 week
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Haploidentical or T-cell depleted graft
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Lack of pre-transplant pulmonary function tests
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Evidence of a prior symptomatic viral respiratory tract infection following transplant, whether treated or not
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Allergy or adverse reaction to any of the study drugs
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Relapse or progression of the underlying malignancy
-
Palliative care
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont) | Montreal | Quebec | Canada | H1T 2M4 |
Sponsors and Collaborators
- Maisonneuve-Rosemont Hospital
- The Canadian Blood and Marrow Transplant Group
Investigators
- Principal Investigator: Elizabeth F Krakow, MD,CM, FRCPC, Maisonneuve-Rosemont Hospital
- Principal Investigator: Sandra Cohen, MD, FRCPC, Maisonneuve-Rosemont Hospital
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- HMR1102