Ventilator Adapters for Combivent Respimat

Study Overview
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Brief Summary
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The general aim of this 1-day, open label, non-randomised, trial is to characterize the performance of two adapter devices designed to permit use of the Respimat® inhaler with patients requiring mechanical ventilation.

Official Title
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Open Label, Non-randomised, 1-day Trial to Characterize the Performance of Two Adapter Devices Designed to Permit Use of the Respimat® Inhaler Device With Patients Requiring Mechanical Ventilation.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Combivent Respimat via tee adapter
* Drug: Combivent Respimat via ventilator adapter


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: All patients or their health care proxy must sign an informed consent consistent with International Conference on Harmonization (ICH)-Good Clinical Practice (GCP) guidelines prior to participation in the trial. Male or female patients, 40 years of age or older Patients must have a pre-admission/pre-ventilation diagnosis of obstructive lung disease (emphysema, chronic bronchitis, or asthma, or a combination thereof), and have a history of treatment with an inhaled bronchodilator. Note that the availability of prior confirmatory spirometry is desirable but not required for participation in the trial Patients must have a clinically relevant and acceptable elective or semi-elective indication for intubation and initiation of mechanical ventilation prior to consideration for trial enrollment. Exclusion criteria: Patients with disease, respiratory or non-respiratory, that is sufficiently unstable (beyond the need for intubation and routine mechanical ventilation) such that their condition will, in the opinion of the investigator (i) put them at risk because of participation in the study, (ii) influence the results of the study [including the assessment of pharmacokinetic parameters], or (iii) cause concern regarding their ability to participate in the study for its duration of one (nominal) day. Patients with any of the following specific conditions: Any systemic or respiratory condition or degree of instability that in the judgment of the principal investigator renders the patient unlikely to safely participate in or complete the study. Investigators are encouraged to contact the trial clinical monitor or team member medicine should there be any question about the suitability of a particular patient for this study. A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists) A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists) Active/unstable cardiac ischemia Unstable or life-threatening cardiac arrhythmia Unstable heart failure (typically Class III or IV) Renal and/or hepatic failure to an extent likely to significantly affect drug metabolism and the consequent effect on the determination of pharmacokinetic parameters as determined by the investigator. Known active tuberculosis Currently under treatment with chemotherapy or radiation therapy for a malignancy. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening. (Note that for the purpose of this trial, commercially available and previously prescribed/administered Combivent Respimat® or Combivent Metered Dose Inhaler (MDI) will not be precluded as investigational.) Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetic acid (EDTA), or any other component of the Respimat® inhalation solution delivery system Pregnant or nursing women Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.However, as subjects in this study will be sedated, on mechanical ventilation for life support and under 24/7 continuous observation in the critical care setting, the use of additional birth control during the study period is not applicable. Patients who are currently participating in another study. Note that patients who have previously been entered into this study and have been tested with one of the two adapters are eligible for re-entry into the trial to be studied with the alternate adapter (after a minimum of 48 hours post completion of the active portion of the trial with the first adapter), and if all inclusion and no exclusion criteria are met.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combivent Respimat via tee adapter<br>Patients (all); previously intubated and ventilated; in need of bronchodilation w/CVT-R via tee adapter | Drug: Combivent Respimat via tee adapter<br>* Patients (all); previously intubated and ventilated; in need of bronchodilation w/CVT-R via tee adapter<br>|
| Experimental: Combivent Respimat - ventilator adapter<br>Patients (all); previously intubated and ventilated; in need of bronchodilation with /CVT-R via ventilator adapter | Drug: Combivent Respimat via ventilator adapter<br>* Patients (all); previously intubated and ventilated; in need of bronchodilation w/CVT-R via ventilator adapter<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose Subtracted Maximum Measured Concentration of Ipratropium | Pre-dose subtracted maximum measured concentration (Cmax) of ipratropium. Standard pharmacokinetic (PK) analyses were not conducted due to a carry-over effect. As a consequence, the pre-specified primary endpoint (maximum measured concentration of ipratropium and albuterol) was not reported. The predose subtracted Cmax was calculated instead of the primary endpoint. | Pre-treatment and 5 minutes (min), 15min, 30min, 60min, 2 hours (h), 4h, 6h after each inhalation of study medication | 
| Pre-dose Subtracted Maximum Measured Concentration of Albuterol | Pre-dose subtracted maximum measured concentration (Cmax) of albuterol. Standard pharmacokinetic (PK) analyses were not conducted due to a carry-over effect. As a consequence, the pre-specified primary endpoint (maximum measured concentration of ipratropium and albuterol) was not reported. The predose subtracted Cmax was calculated instead of the primary endpoint. | Pre-treatment and 5 minutes (min), 15min, 30min, 60min, 2 hours (h), 4h, 6h after each inhalation of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve Over the Time Interval From 0 to 6 Hour (AUC 0-6) of Ipratropium and Albuterol | Area under the concentration-time curve over the time interval from 0 to 6 hour (AUC 0-6) of ipratropium and albuterol. This secondary endpoint was not calculated due to a carry-over effect. | Pre-treatment and 5 minutes (min), 15min, 30min, 60min, 2 hours (h), 4h, 6h after each inhalation of study medication |