Individualized Dosing Schedule of Inhaled Bronchodilator for Endotracheally Intubated COPD Patients

NCT ID: NCT01933984

Last Updated: 2020-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2019-01-31

Brief 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.

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.

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Individualized dosing

• Ventilator support
• Determining personal target airway resistance
• Bronchodilator:Salmeterol/fluticasone 4 puffs inhalation every 12 hours until ventilator discontinuation or the 28th day if ventilator-dependent
• Bronchodilator:Ipatropium/salbutamol 1 vial inhalation every 6 hours for the first 3 days
• Steroid:Methylprednisolone 40 mg intravenous injection every 8 hours for the first 3 days
• Additional broncho-dilators inhalation: Salmeterol/fluticasone (Seretide) 4 puffs plus fenoterol (Berotec) 4 puffs inhalation if personal target airway resistance (measured every 8 hours) not met (until ventilator discontinuation or the 28th day if ventilator-dependent)

Group Type: EXPERIMENTAL

Bronchodilators inhalation

Intervention Type: DRUG

Salmeterol/fluticasone (Seretide Evohaler) 4 puffs plus fenoterol (Berotec)(0.1mg/puff) 4 puffs inhalation when target airway resistance, measured every 8 hours, not met

Fixed dosing

• Ventilator support
• Determining personal target airway resistance
• Bronchodilator:Salmeterol/fluticasone 4 puffs inhalation every 12 hours until ventilator discontinuation or the 28th day if ventilator-dependent
• Bronchodilator:Ipatropium/salbutamol 1 vial inhalation every 6 hours for the first 3 days
• Steroid:Methylprednisolone 40 mg intravenous injection every 8 hours for the first 3 days
• No additional bronchodilator given if personal target airway resistance (measured every 8 hours) not met

Group Type: ACTIVE_COMPARATOR

Bronchodilators inhalation

Intervention Type: DRUG

Salmeterol/fluticasone (Seretide Evohaler) 4 puffs plus fenoterol (Berotec)(0.1mg/puff) 4 puffs inhalation when target airway resistance, measured every 8 hours, not met

Interventions

Bronchodilators inhalation

Salmeterol/fluticasone (Seretide Evohaler) 4 puffs plus fenoterol (Berotec)(0.1mg/puff) 4 puffs inhalation when target airway resistance, measured every 8 hours, not met

Intervention Type: DRUG

Other Intervention Names

Salmeterol/fluticasone (Seretide Evohaler); fenoterol (Berotec)(0.1mg/puff)

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shin-hwar Wu

OTHER

Sponsor Role: lead

Responsible Party

Shin-hwar Wu

Attending physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Shin-hwar Wu

Role: PRINCIPAL_INVESTIGATOR

Changhua Christian Hospital

Locations

Changhua Christian Hospital

Changhua, Taiwan, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 19014570 (View on PubMed)

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. doi: 10.1164/ajrccm/141.2.440.

Reference Type: BACKGROUND

PMID: 2154154 (View on PubMed)

Aerosol consensus statement. Consensus Conference on Aerosol Delivery. Chest. 1991 Oct;100(4):1106-9. No abstract available.

Reference Type: BACKGROUND

PMID: 1914568 (View on PubMed)

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. doi: 10.1164/ajrccm.154.2.8756811.

Reference Type: BACKGROUND

PMID: 8756811 (View on PubMed)

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. doi: 10.1038/clpt.1981.154. No abstract available.

Reference Type: BACKGROUND

PMID: 7249508 (View on PubMed)

Wu SH, Shyu LJ, Li CH, Yu CH, Chen HC, Kor CT, Wang CH, Lin KH. Better airway resistance reduction profile in intubated COPD patients by personalized bronchodilator dosing: A pilot randomized control trial. Pulm Pharmacol Ther. 2018 Apr;49:134-139. doi: 10.1016/j.pupt.2018.02.004. Epub 2018 Feb 21.

Reference Type: DERIVED

PMID: 29474893 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

102-CCH-IRP-017

Identifier Type: -

Identifier Source: org_study_id