A RCT to Compare the Effectiveness of Nebulized Anticholinergics for Cough Suppression During Flexible Bronchoscopy (NAFCOF)

A Randomized, Double-blind, Placebo-controlled Trial to Compare the Effectiveness of Nebulized Anticholinergics for Cough Suppression During Flexible Bronchoscopy

No study has examined the role of inhaled glycopyrrolate on mucus secretion. We hypothesize that nebulized glycopyrrolate will improve bronchoscopy procedure by effectively suppressing airway mucus secretion, thereby decreasing cough, and thus improving patient comfort during bronchoscopy. In this study, we aim to compare the efficacy of nebulized glycopyrrolate versus nebulized ipratropium in suppression of cough during flexible bronchoscopy.

Study Overview

• Status: Not yet recruiting
• Conditions: Subjects Undergoing Flexible Bronchoscopy
• Intervention / Treatment: Drug: Glycopyrronium; Drug: Ipratropium; Other: Saline

Detailed Description

Bronchoscopy is a minimally invasive endoscopic technique for direct visualization of airways, with diagnostic and therapeutic intent. In 1897, Killian laid the foundation of bronchoscopy by extracting an animal bone from the right main bronchus of a farmer using rigid esophagoscope. In 1966, Shigeto Ikeda developed a prototype of flexible bronchoscope. Since its inception, flexible bronchoscope has undergone advancements in design and technology. The technological advancements in the recent decades have improved diagnostic yield and safety, with low morbidity and mortality. Unfortunately, the occurrence of cough during flexible bronchoscopy makes the procedure difficult and increases procedure time with patient discomfort.

Owing to the lack of clinical benefits and possible hemodynamic changes, the British Thoracic Society and Joint Indian Chest Society recommend not to use anticholinergic premedication via the parenteral route for preventing cough before bronchoscopy.

bronchoscopy. A few studies have evaluated inhaled anticholinergic premedication. Inoue et al. (in 1994) studied the effects of inhaled ipratropium bromide on bronchoconstriction in 29 subjects underwent for diagnostic bronchoscopy. They concluded that ipratropium protects against the deleterious effects resulting from topical lidocaine anesthesia during bronchoscopy. Wang et al. evaluated the efficacy of ipratropium bromide in 250 patients in a placebo-controlled trial. They reported that nebulized ipratropium bromide could reduce airway secretions and patient discomfort.

To our knowledge, no study has examined the role of inhaled glycopyrrolate on mucus secretion. We hypothesize that nebulized glycopyrrolate will improve bronchoscopy procedure by effectively suppressing airway mucus secretion, thereby decreasing cough, and thus improving patient comfort during bronchoscopy.

In this study, we aim to compare the efficacy of nebulized glycopyrrolate versus nebulized ipratropium in suppression of cough during flexible bronchoscopy.

• Study Type: Interventional
• Enrollment (Estimated): 1050
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ritesh Agarwal; Phone Number: 7087007625; Email: agarwal.ritesh@outlook.in
• Study Contact Backup: Name: Inderpaul Sehgal; Phone Number: 7087007625; Email: inderpgi@outlook.com

Study Locations

• India
  • Chandigarh, India, 160012
    • Bronchoscopy suite, PGIMER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Consecutive patients with indication for flexible bronchoscopy will be enrolled in the study if they meet all the following criteria:

• age ≥18 years
• hemodynamically stable
• willing to provide a written informed consent

Exclusion Criteria: Patients with any of the following will be excluded:

• intubated or tracheostomized patients
• patients with airway stent in situ
• patients with a history of glaucoma
• baseline oxygen saturation <90%
• patients with hemodynamic instability (SBP <90 mm Hg)
• patients undergoing sedation for bronchoscopy
• failure to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glycopyrronium; Nebulized glycopyrronium 50 mcg (2 ml) administered via a jet nebulizer over 10 minutes	Drug: Glycopyrronium; Nebulized glycopyrronium 50 mcg
Active Comparator: Ipratropium; Nebulized ipratropium bromide 500 mcg (2 ml) administered via a jet nebulizer over 10 minutes	Drug: Ipratropium; Nebulized iptratropium 500 mcg
Placebo Comparator: Saline; Nebulized saline 0.9% (2 ml) administered via a jet nebulizer over 10 minutes	Other: Saline; 0.9% saline 2 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cough count	Objectively measured using condenser microphone and voice recording application though a smartphone	Intra-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operator-estimated airway secretion	Recorded as: almost none, needing saline to wash out, and excessive, making it difficult to visualize the airways and requires 5 ml aliquots of saline	Intra-procedure
Operator-rated secretions on a visual analogue scale (VAS)	100 mm VAS anchored as no secretion at one and maximal secretions at the other	Immedidate post-procedure
Operator-rated cough intensity on a visual analogue scale (VAS)	100 mm VAS anchored as no cough at one and maximal cough at the other	Immedidate post-procedure
Patient-rated comfort on a visual analogue scale (VAS)	100 mm VAS anchored as maximal comfort at one and maximal discomfort at the other	Immedidate post-procedure
Adverse reactions	Arrhythmia, glaucoma, nausea, headache	1-hour post-procedure

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Study record dates

Study Major Dates

• Study Start (Estimated): April 24, 2024
• Primary Completion (Estimated): April 25, 2025
• Study Completion (Estimated): June 15, 2025

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Ipratropium
• Other Study ID Numbers: Int/IEC/2024/SPL-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No