Rapamune Improves Outcomes of Severe H1N1 Pneumonia

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoxemia; H1N1 Pneumonia
• Intervention / Treatment: Drug: Sirolimus (Rapamune 2mg/day, Pfizer)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: with Rapamune treatment; 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); Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days.
Placebo Comparator: Without Rapamune treatment.; 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); Sirolimus (Rapamune 2mg/day, Pfizer) or not for a course of 14 days.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Study Chair: TSANG-TANG Hsieh, MD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: June 13, 2012
• First Submitted That Met QC Criteria: June 14, 2012
• First Posted (Estimate): June 15, 2012

Study Record Updates

• Last Update Posted (Estimate): June 15, 2012
• Last Update Submitted That Met QC Criteria: June 14, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: H1N1 patients with severe hypoxemia requiring ventilator support
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Signs and Symptoms, Respiratory; Pneumonia; Hypoxia; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: IRB:100-2433C