Individualized Dosing Schedule of Inhaled Bronchodilator for Endotracheally Intubated COPD Patients
Information source: Changhua Christian Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Chronic Obstructive Pulmonary Disease
Intervention: salmeterol/fluticasone (Drug); ipatropium/salbutamol (Drug); Methylprednisolone (Drug); Additional broncho-dilators inhalation (Drug); Determining personal target airway resistance (Other); Ventilator support (Device)
Phase: N/A
Status: Recruiting
Sponsored by: Shin-hwar Wu Official(s) and/or principal investigator(s): Shin-hwar Wu, Principal Investigator, Affiliation: Changhua Christian Hospital
Overall contact: Shin-hwar Wu, Phone: 886-4-723-8595, Ext: 3978, Email: 126366@cch.org.tw
Summary
This study evaluates whether individualized dosing schedule of inhaled bronchodilator is
more effective than fixed dosing in reducing airway resistance of intubated COPD patients.
Clinical Details
Official title: Individualized Dosing Schedule of Inhaled Bronchodilator for Endotracheally Intubated Chronic Obstructive Pulmonary Disease Patients
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: ∆Raw (the difference between measured and target airway resistance)Rapidity of ∆Raw change
Secondary outcome: number of ventilator-free days from day 1 to 28Percentage of breathing without assistance by day 28 number of episode of nosocomial pneumonia Number of total puff of rescue short-acting bronchodilator number of drug-related adverse effect Mortality rate
Detailed description:
*Study Design
- This is an open-label, randomized controlled study comparing individualized versus
fixed bronchodilator dosing schedule for patients with COPD with acute respiratory
failure.
*Patients Enrollment
- We will collect 100 patients just admitted to the intensive care unit of Changhua
Christian Hospital (Changhua, Taiwan) due to COPD with acute respiratory failure. All
participants will be randomly assigned to either group according to a
computer-generated allocation sequence in block size of 4 patients.
*Airway Resistance (Raw) Determination
- Enrolled patients will be ventilated by either AVEA (CareFusion, Yorba Linda, CA,
USA),e500 (Newport Medical Instrument Inc. CA, USA) or Eivta 4 (Drager) ventilator.
When evaluating Raw, the ventilator settings will be transiently switched to volume
control mode with fixed tidal volume (500 ml) and constant flow (with a rate of 60
L/min). Plateau pressure is measured by manually controlled end-inspiratory pause12.
Every effort will be exercised to avoid excessive airway secretion or patient agitation
during measurement. Each measurement will be repeated three times with an interval of
at lease 1 minute and calculate their average. Raw will be calculated by an equation of
(peak inspiratory pressure - plateau pressure)/flow. After each measurement, the
ventilator will soon be reverted to its usual settings. Raw will be routinely
determined every 8 hours for 28 days if the ventilator is not discontinued.
*Technique of Metered Dose Inhaler (MDI) administration through endotracheal tube
- The technique basically follows the recommendation of Dhand and Guntur. Airway
secretions should be sucked out before drug administration. Heat moisture exchanger,
but not humidifier, is removed. After shaking and warming MDI to hand temperature, the
canister is connected to an AeroChamber HC MV spacer (Trudell Medical International,
London, Canada) placed in the inspiratory limb of ventilator circuit 15 cm away from
the endotracheal tube. Actuation is synchronized with the initiation of inspiration.
Each actuation is at least 15 second apart.
*Personal Target Raw Determination
- The target Raw of each patient should be determined within 72 hours after their
admission to intensive care unit. After confirming no inhaled bronchodilator given in
preceding 2 hours (for fenoterol) or 12 hours (for salmeterol/fluticasone), we will
deliver 3 consecutive doses of 4 puffs, 8 puffs and 16 puffs of fenoterol MDI (100
mcg/puff, Berotec;Boehringer Ingelheim, Ingelheim, Germany) inhalation with each dose
15 minutes apart. The Raw measured 15 minutes later is assigned as this patient's
personal target Raw.
*Bronchodilator Delivery Schedule
- Each patient will routinely receive 4 puffs of 25 mcg salmeterol /250 mcg fluticasone
(Seretide Evohaler 250; GlaxoSmithKline Inc. Evreux, France) every 12 hours until the
discontinuation of ventilator. Each patient will also routinely receive 1 vial of
Combivent (ipatropium bromide 0. 5 mg and salbutamol sulfate 2. 5 mg) every 6 hours and
be injected with intravenous methylprednisolone 40mg every 8 hours in the initial 3
days. The use of short acting bronchodilator in an as-needed basis is not restricted.
According to the Raw data determined every 8 hours, individualized dosing group will
receive an additional 4 puffs of 25 mcg salmeterol /250 mcg fluticasone plus 4 puffs of
fenoterol if the value is higher than personal target Raw (Once it coincides with
regular dosing period of salmeterol/fluticasone, only fenoterol will be added). No such
extra dose will be given to fixed dosing (control) group regardless of Raw value.
*Statistical Analysis
- Student's t test will be used to compare ∆Raw of both groups. For the comparisons of
other continuous variables without distribution normality, Wilcoxon rank sum test will
be used. When comparing two categorical variables, Chi-square or Fisher's exact test
will be used when appropriate. A P value of less than 0. 05 is considered significant.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- chronic obstructive pulmonary disease
- acute respiratory failure under ventilator support for less than 72 hours
- endotracheal tube inserted
Exclusion Criteria:
- confirmed asthma
- Acute Physiology and Chronic Health Evaluation II score over 35
- a co-morbidity of septic shock
Locations and Contacts
Shin-hwar Wu, Phone: 886-4-723-8595, Ext: 3978, Email: 126366@cch.org.tw
Changhua Christian Hospital, Changhua, Taiwan 50006, China; Recruiting Shin-hwar Wu, Phone: 886-4-723-8595, Ext: 3978, Email: 126366@cch.org.tw Kai-huang Lin, Phone: 886-4-723-8595, Ext: 3971, Email: 54407@cch.org.tw Shin-hwar Wu, Principal Investigator Kai-huang Lin, Sub-Investigator Chin-hsing Li, Sub-Investigator Lih-jen Shyu, Sub-Investigator
Additional Information
Related publications: Fuller HD, Dolovich MB, Posmituck G, Pack WW, Newhouse MT. Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Comparison of dose to the lungs. Am Rev Respir Dis. 1990 Feb;141(2):440-4. Aerosol consensus statement. Consensus Conference on Aerosol Delivery. Chest. 1991 Oct;100(4):1106-9. Review. Dhand R, Duarte AG, Jubran A, Jenne JW, Fink JB, Fahey PJ, Tobin MJ. Dose-response to bronchodilator delivered by metered-dose inhaler in ventilator-supported patients. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):388-93. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2):239-45. Malliotakis P, Linardakis M, Gavriilidis G, Georgopoulos D. Duration of salmeterol-induced bronchodilation in mechanically ventilated chronic obstructive pulmonary disease patients: a prospective clinical study. Crit Care. 2008;12(6):R140. doi: 10.1186/cc7117. Epub 2008 Nov 14.
Starting date: August 2013
Last updated: September 9, 2013
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