Rapamune Improves Outcomes of Severe H1N1 Pneumonia

Chang Gung Medical Foundation

Status and phase: Completed; Phase 2

Conditions: H1N1 Pneumonia; Hypoxemia

Treatments: Drug: Sirolimus (Rapamune 2mg/day, Pfizer)

Study type: Interventional

Funder types: Other

Identifiers

NCT01620307

IRB:100-2433C

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 patients

Sex: All

Ages: 20 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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38 participants in 2 patient groups, including a placebo group

with Rapamune treatment

Active Comparator group

Description:

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.

Treatment:

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

Without Rapamune treatment.

Placebo Comparator group

Description:

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.

Treatment:

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