COPD Aerosol Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers

Study Overview
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Brief Summary
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The purpose of this study is to compare drug delivery and lung function after treatment with formoterol from a nebulizer versus a dry powder inhaler (DPI) in patients recovering from severe exacerbations of COPD. This is to determine if one device is superior in providing better lung function and drug deposition in this clinical setting.

Official Title
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A Randomized, Double-Dummy, Crossover, Single-Center Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers in the Treatment of Patients Recovering From Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD Exacerbation

Intervention / Treatment
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* Drug: Formoterol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current or past cigarette smoking history of >/= 10 pack-years. FEV1/FVC ratio </= 70%. Known diagnosis of COPD. Current hospitalization for a primary diagnosis of acute exacerbation of COPD. Must be able to understand and willing to sign an informed consent document. Exclusion Criteria: On a ventilator or mask ventilation. Allergy or contraindication to Formoterol use. Marked QTc prolongation (> 450 ms). Liver cirrhosis or chronic renal insufficiency (serum creatinine > 2 mg/dL). Atrial fibrillation with rapid ventricular response (heart rate > 110 bpm) or ventricular arrhythmia (frequent PVCs, ventricular tachycardia). Acute myocardial infarction within 12 weeks of patient study registration. Known pulmonary embolism. Known or suspected lung cancer. Known neuromuscular disease, stroke with residual hemiparesis, or untreated Parkinsonism Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or sub dermal implants). Inability to understand instructions. Participation in another investigational drug clinical trial within 30 days of patient study registration.

Ages Eligible for Study
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Minimum Age: 40 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Formoterol via DPI then Formoterol via nebulizer<br>Group A: Received Formoterol 12 µg via DPI and placebo via nebulizer at treatment visit #1, and Formoterol 20 µg (solution form) via nebulizer and placebo via DPI at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2. | Drug: Formoterol<br>* Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.<br>* Other names: PERFOROMIST;Other: Placebo<br>* Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.<br>* Other names: Normal Saline;|
| Active Comparator: Formoterol via nebulizer then Formoterol via DPI<br>Group B: Received Formoterol 20 µg (solution form) via nebulizer and placebo via a DPI at treatment visit #1, and Formoterol 12 µg via a DPI with placebo via nebulizer at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2. | Drug: Formoterol<br>* Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.<br>* Other names: PERFOROMIST;Other: Placebo<br>* Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference Between the Values of Area Under the Response Curve for FEV1 | The difference between the values of area under the response curve for FEV1 from baseline through four hours (AUC FEV1 0-4h) after inhalation of formoterol with a nebulizer or a dry powder inhaler. | Baseline through study completion (visit 1 through visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol | Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 will be recorded. Subjects will be dosed with formoterol. Serial FEV1 assessments will completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement can be recorded. A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result. | From pre-dose formoterol (baseline 0hrs) to 30 minutes, 1,2, and 4 hours post dose at visit 1 and measured again at visit 2 | 
| Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol | Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects was dosed with formoterol. Serial FEV1 assessments were completed, and recorded at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so serial FEV1 measurements could be recorded. | Measured at visit 1 and visit 2 after dosing and all FEV1 testing has been completed | 
| Peak FEV1 Between the Two Devices (Nebulizer and DPI) | Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement could recorded. 5. Peak measurements from visit 1 and visit 2 will be compared for any significant change in FEV1 values. | Measured from Start of visit 1 until the completion of visit 2 | 
| Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol | Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FEV1 values were recorded. A percentage of change from baseline FEV1 to each serial measurement of FEV1 was collected. The % of change at each time point was then used to get a measure of overall percentage change of the predicted FEV1 value. | Baseline through study completion (visit 1 through visit 2) | 
| Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol | Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Data was all time points were used to obtain the total area under the curve | Measured at visit 1 and again at the end of visit 2 | 
| Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol | A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. A percentage of change between the baseline and peak FVC will be recorded for this outcome measure. | Measured at visit 1 and again at the end of visit 2 | 
| Peak FVC Between the Two Devices (Nebulizer and DPI) | Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Peak FVC was recorded for this outcome measure and compared amongst groups. | Peak FVC at visit 1 will be compared to the peak FVC at visit 2 for any significant change. | 
| Change in Dyspnea Based on the Borg Dyspnea Scale for Shortness of Breath (Pre-dose Administration and 60 Minutes After Inhalation of Formoterol With a Nebulizer or a DPI) | The Shortness of Breath Modified Borg Dyspnea Scale The scale goes from 0-10, zero meaning no difficulty breathing and ten meaning maximal difficulty. A decrease of score indicates an improvement. Patients were asked to complete the scale pre-dose and again one hour post formoterol dose. This was completed at both visit 1 and visit 2. The value recorded was the difference between the baseline value and the post 60 minute value. | Measured at visit 1 and again at the end of visit 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, chronic obstructive pulmonary disease