N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of COPD

November 14, 2023 updated by: Kwok Wang Chun, Queen Mary Hospital, Hong Kong

A Double-Blind Randomized Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Patients with Chronic obstructive pulmonary disease (COPD) experience gradually deteriorating lung function, which may be complicated by acute exacerbations. N- acetylcysteine (NAC) is frequently used in patients with COPD as a mucolytic. Besides its mucolytic effects, high-dose NAC has additional benefits in patients with stable COPD, including improving lung function and reducing exacerbations. Studies on the dose-dependent effects of NAC in COPD patients showed a high dose of NAC was needed to achieve its antioxidant effects and clinical benefits in COPD patients, whereas a dose of 600 mg once daily was not able to increase glutathione levels. According to a study conducted in Hong Kong on patients with stable COPD, 1 year of treatment with high-dose NAC at 600 mg twice daily improved small airways function in terms of forced expiratory flow and forced oscillation technique, and also significantly reduced exacerbation frequency with a decreasing trend in admission rate. In a meta-analysis, patients treated with NAC had significantly and consistently fewer exacerbations of COPD. The role of NAC was examined in a Delphi consensus study involving 53 COPD experts from 12 countries. Respondents agreed that regular treatment with mucolytic agents could effectively decrease the frequency of exacerbations and the duration of mild-to-moderate exacerbations, while delaying the time to first exacerbation and increasing symptom-free time in COPD patients. The panel also approved the doses of NAC with favourable side effect profiles to be recommended for regular use in patients with a bronchitic phenotype.

However, there have been conflicting results regarding the efficacy of NAC for treating acute exacerbation of COPD. NAC has not been included as an adjunct for the treatment of COPD exacerbation in international guidelines. As NAC is relatively low cost, readily available, and has a favourable side effect profile as a treatment for COPD exacerbation, it is important to properly assess the clinical benefits of NAC as an adjunct to standard medical treatments to hasten recovery. This study is a double-blind randomised controlled trial on NAC as an adjunctive treatment for acute COPD exacerbation. It will assess the role of NAC in the treatment of acute COPD exacerbation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The aim of the study is to assess the role of NAC in the treatment of acute COPD exacerbation in terms of clinical, physiological, and laboratory parameters, including PaO2, PaO2/FiO2 ratio, PaCO2, SaO2, end tidal CO2, length of stay, coughing, wheezing, dyspnoea, need for supplemental oxygen sputum volume, FEV1, and blood inflammatory markers.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
        • Contact:
          • Wang Chun Kwok

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Aged 40 years or above, either male or female.

  2. Patients who are current or ex-smokers

    • Ever-smoker is defined as having smoked at least one cigarette, pipe, water pipe, cigars, or hand rolled cigarettes a day for 1 or more years.

  3. Patients with a pre-existing diagnosis of COPD admitted to the general medical and respiratory subspecialty wards for acute COPD exacerbation

    • COPD is defined as dyspnoea and/or chronic productive cough with spirometry confirmation of persistent airflow limitation at FEV1/FVC less than 70%.
    • COPD acute exacerbation is defined as an acute increase in symptoms (one or more of the following: cough frequency and severity, sputum production, dyspnoea) beyond normal day-to-day variations leading to a change in medication.
  4. Patients who consent to join this clinical trial

Exclusion Criteria:

  1. Patients who are on long-term NAC treatment
  2. Patients who are not able to take NAC including drug allergy
  3. Patients with other co-existing respiratory diseases including but not limited to asthma, interstitial lung diseases, and bronchiectasis
  4. Patients on non-invasive or invasive mechanical ventilation where oral medication is not allowed
  5. Patients on long term macrolide treatment
  6. Patients on macrolide as antibiotics for COPD exacerbation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Patients will be randomized to receive placebo for 1 week. The randomization will be done via computer software with half receive placebo. Patients will also be given standard treatment for your COPD exacerbation and can continue the use of usual inhalers for COPD.
Experimental: N-acetylcysteine
Drug: N-acetylcysteine
Patients will be randomized to receive oral N-acetylcysteine at 600 mg twice daily for 1 week. The randomization will be done via computer software with half of the patients randomized to receive NAC. Patients will also be given standard treatment for your COPD exacerbation and can continue the use of usual inhalers for COPD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The difference in mean PaO2 and the change of PaO2
Time Frame: day 7; from day 0 to day 7
The co-primary endpoint of interest is the difference in mean PaO2 on day 7 of treatment and the change of PaO2 from day 0 to day 7.
day 7; from day 0 to day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change in PaO2/FiO2 ratio
Time Frame: from baseline to day 7
The change in PaO2/FiO2 ratio from baseline to day 7
from baseline to day 7
The time to wean off supplemental oxygen
Time Frame: from baseline to day 7
from baseline to day 7
The length of stay
Time Frame: from baseline to day 7
from baseline to day 7
The blood inflammatory markers
Time Frame: from baseline to day 7
Blood inflammatory markers including white cell count, neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and high-sensitivity CRP (hs-CRP) will also be measured, total 20 mL of blood will be taken. Blood inflammatory markers including white cell count, neutrophil count, ESR, CRP, and hs-CRP will be measured on days 4 and 7. The blood tests arranged for the patients are the basic blood tests for clinical management of COPD exacerbation and it does not involve extra blood testing for the patients.
from baseline to day 7
The 28- and 90-day mortality
Time Frame: from baseline to 28- and 90-day
from baseline to 28- and 90-day
The change in sputum volume
Time Frame: from baseline to day 7
The change in sputum volume on days 4 and 7
from baseline to day 7
The Change in COPD Assessment Test (CAT) score
Time Frame: from baseline to day 7
The change in CAT score on days 4 and 7. CAT score has a scoring range of 0 to 40. Higher scores indicating the COPD has a greater impact on overall health outcome.
from baseline to day 7
The Change in Leicester cough questionnaire (LCQ) score
Time Frame: from baseline to day 7
The change in LCQ score on days 4 and 7. The LCQ is assessing 3 domains (physical, psychological and social). The total score range is 3-21 and domain scores range from 1-7. Higher scores indicates a better quality of life.
from baseline to day 7
The Change in the grade of wheeze assessment (Grading system)
Time Frame: from baseline to day 7
The change in grade of wheeze on days 4 and 7. Grade of wheeze, to be assessed by the PI or Co-I, is a simple bedside assessment can that can assess the severity of COPD. This could allow a simple assessment of the respiratory status for the patients with COPD exacerbation. There will be 3 grades; higher grade indicates a more severe respiratory symptoms.
from baseline to day 7
The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale
Time Frame: from baseline to day 7
The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale on days 4 and 7. The mMRC scale ranges from grade 0 to 4. Higher grade indicates a higher degree of baseline functional disability due to dyspnoea.
from baseline to day 7
The change in FEV1
Time Frame: from baseline to day 7
The change in FEV1 on days 4 and 7
from baseline to day 7
The change in end tidal CO2
Time Frame: from baseline to day 7
The change in end tidal CO2 on days 4 and 7
from baseline to day 7
The change in SaO2
Time Frame: from baseline to day 7
The change in SaO2 on days 4 and 7
from baseline to day 7
The change in PaCO2
Time Frame: from baseline to day 7
The change in PaCO2 on day 7
from baseline to day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen Mary Hospital, Hong Kong

Investigators

  • Principal Investigator: Wang Chun Kwok, MBBS, Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 18, 2023

Primary Completion (Estimated)

September 30, 2025

Study Completion (Estimated)

September 30, 2025

Study Registration Dates

First Submitted

January 11, 2023

First Submitted That Met QC Criteria

January 20, 2023

First Posted (Actual)

January 31, 2023

Study Record Updates

Last Update Posted (Estimated)

November 17, 2023

Last Update Submitted That Met QC Criteria

November 14, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 22-710

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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