Rapamune Improves Outcomes of Severe H1N1 Pneumonia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chung Fu-Tsai, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01620307
First received: June 13, 2012
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
H1N1 Pneumonia
Hypoxemia
Drug: Sirolimus (Rapamune 2mg/day, Pfizer)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Treatment With a mTOR Inhibitor, Rapamune Improves Outcomes of Severe H1N1 Pneumonia With Acute Respiratory Failure

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • liberation of ventilator [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • necessity of Extracorporeal membrane oxygenation(ECMO) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    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


Enrollment: 38
Study Start Date: June 2009
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   20 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01620307

Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Study Chair: Tsang-Tang Hsieh, MD Chang Gung Memorial Hospital
  More Information

No publications provided

Responsible Party: Chung Fu-Tsai, Attending physician, Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01620307     History of Changes
Other Study ID Numbers: IRB:100-2433C
Study First Received: June 13, 2012
Last Updated: June 14, 2012
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Chang Gung Memorial Hospital:
H1N1 patients with severe hypoxemia requiring ventilator support

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014