Rapamune Improves Outcomes of Severe H1N1 Pneumonia

Study Overview
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Brief Summary
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Severe H1N1 pneumonia with acute respiratory failure shows hyperactive immune cells infiltration of lung. Rapamune, a mTOR inhibitor, modulates the immune response by blocking activation of T- and B-cells. To investigate the clinical efficiency of rapamune in severe H1N1 pneumonia with respiratory failure, this study was conducted.

Detailed Description
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From 2009 winter to 2011 spring, patients with flu-like symptoms in Chang Gung Memorial Hospital were screened by rapid antigen test and influenza subtype was confirmed by polymerization chain reaction (PCR). 38 H1N1 patients with severe hypoxemia [alveolar-arterial oxygen gradient, (A-a) O2 gradient, > 200 mmHg] requiring ventilator support were randomized to receive Rapamune (2mg/day) or not. Patients were then randomized to receive either Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days. The outcome variables include liberation of ventilator, ICU mortality, necessity of ECMO, Sequential Organ Failure Assessment (SOFA) score and complications after admission to ICU were recorded. SOFA score composed of scores from six organ systems, graded from 0 to 4 according to the degree of dysfunction/failure.

Official Title
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Adjuvant Treatment With a mTOR Inhibitor, Rapamune Improves Outcomes of Severe H1N1 Pneumonia With Acute Respiratory Failure

Conditions
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H1N1 Pneumonia, Hypoxemia

Intervention / Treatment
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* Drug: Sirolimus (Rapamune 2mg/day, Pfizer)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: H1N1 patients with severe hypoxemia [alveolar-arterial oxygen gradient, (A-a) O2 gradient, > 200 mmHg] requiring ventilator support were included to randomization. Exclusion Criteria: severity of illness and multiple organ dysfunction (MOD) were assessed within 24 hours of ICU admission.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: with Rapamune treatment<br>All patients were treated with Oseltamivir (Tamiflu, Roche) 50 mg twice a day for 10 days and oral prednisolone 20 mg/day for 14 days. At ICU admission, patients started on empiric antimicrobial therapy with moxifloxacin 500 mg per day until results of microbiological studies were available. Each patient received best support treatment including mechanical ventilator, fluid resuscitation, gastrointestinal and thromboembolic prophylaxis, and enteral nutrition for most aspects of care. After radomization, patients were received Sirolimus (Rapamune 2mg/day, Pfizer)for a course of 14 days. | Drug: Sirolimus (Rapamune 2mg/day, Pfizer)<br>* Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days.<br>|
| Placebo Comparator: Without Rapamune treatment.<br>All patients were treated with Oseltamivir (Tamiflu, Roche) 50 mg twice a day for 10 days and oral prednisolone 20 mg/day for 14 days. At ICU admission, patients started on empiric antimicrobial therapy with moxifloxacin 500 mg per day until results of microbiological studies were available. Each patient received best support treatment including mechanical ventilator, fluid resuscitation, gastrointestinal and thromboembolic prophylaxis, and enteral nutrition for most aspects of care. After radomization, patients were not to receive Sirolimus (Rapamune 2mg/day, Pfizer)for a course of 14 days. | Drug: Sirolimus (Rapamune 2mg/day, Pfizer)<br>* Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liberation of ventilator | Patients were then randomized to receive either Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days. Ventilator management was previously described. The ventilator liberation rate is primary outcome. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| necessity of Extracorporeal membrane oxygenation(ECMO) | Patients were then randomized to receive either Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days. Ventilator management was previously described.Extracorporeal membrane oxygenation (ECMO) was used in patients with severe refractory hypoxemia | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H1N1 patients with severe hypoxemia requiring ventilator support