Chronic Obstructive Pulmonary DiseasePhase 3NCT05706402
N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of COPD
A Phase 3 study testing N-acetylcysteine in people with Chronic Obstructive Pulmonary Disease, run by Queen Mary Hospital, Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteHong Kong
- Study dates
- 18 Sep 2023to 30 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 40 years or above, either male or female.
- 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.
- 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.
- Patients who consent to join this clinical trial
Who cannot join
- Patients who are on long-term NAC treatment
- Patients who are not able to take NAC including drug allergy
- Patients with other co-existing respiratory diseases including but not limited to asthma, interstitial lung diseases, and bronchiectasis
- Patients on non-invasive or invasive mechanical ventilation where oral medication is not allowed
- Patients on long term macrolide treatment
- Patients on macrolide as antibiotics for COPD exacerbation
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Queen Mary Hospital
Hong Kong
Wang Chun Kwok
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- N-acetylcysteine, Placebo
- Keywords
- N-acetylcysteine, Chronic Obstructive Pulmonary Disease, Chronic Obstructive Pulmonary Disease exacerbation, Clinical trial
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| N-acetylcysteine | Experimental | Not described Receives: Drug: N-acetylcysteine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in mean PaO2 and the change of PaO2
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.
Measured: day 7; from day 0 to day 7
Secondary outcomes (14)
The change in PaO2/FiO2 ratio
The change in PaO2/FiO2 ratio from baseline to day 7
Measured: from baseline to day 7
The change in sputum volume
The change in sputum volume on days 4 and 7
Measured: from baseline to day 7
The Change in COPD Assessment Test (CAT) score
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.
Measured: from baseline to day 7
The Change in Leicester cough questionnaire (LCQ) score
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.
Measured: from baseline to day 7
The Change in the grade of wheeze assessment (Grading system)
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.
Measured: from baseline to day 7
The change in grade of dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale
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.
Measured: from baseline to day 7
The change in FEV1
The change in FEV1 on days 4 and 7
Measured: from baseline to day 7
The change in end tidal CO2
The change in end tidal CO2 on days 4 and 7
Measured: from baseline to day 7
The change in SaO2
The change in SaO2 on days 4 and 7
Measured: from baseline to day 7
The change in PaCO2
The change in PaCO2 on day 7
Measured: from baseline to day 7
The time to wean off supplemental oxygen
Measured: from baseline to day 7
The length of stay
Measured: from baseline to day 7
The blood inflammatory markers
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.
Measured: from baseline to day 7
The 28- and 90-day mortality
Measured: from baseline to 28- and 90-day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2023
- Study start18 Sep 2023
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a double-blind randomised controlled trial on NAC as an adjunctive treatment for acute COPD exacerbation. The randomization will be done via computer software with half of the patients randomized to received oral NAC (600 mg twice daily) and half receive placebo, with randomization ratio being 1 to 1. Patients in the two randomised group will be asked to participate in the study for a maximum of 1 week.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen Mary Hospital, Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kwok Wang Chun, Queen Mary Hospital, Hong Kong
- Investigators
- Wang Chun Kwok, MBBS, Principal investigator, Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05706402
- Sponsor's protocol ID
- UW 22-710
- Status last verified
- Nov 2023
- First submitted
- 11 Jan 2023
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kwok WC, Chan SKS, Chiang KY, Ho CMJ. A double-blind randomized controlled trial of N-acetylcysteine (NAC) for the treatment of acute exacerbation of chronic obstructive pulmonary disease. Respirol Case Rep. 2024 Aug 6;12(8):e01449. doi: 10.1002/rcr2.1449. eCollection 2024 Aug.
PubMed 39108325
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Randomized Controlled Trial of N-acetylcysteine (NAC) for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT05706402
- Acronym / sponsor ID
- UW 22-710
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- N-acetylcysteine, Chronic Obstructive Pulmonary Disease, Chronic Obstructive Pulmonary Disease exacerbation, Clinical trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Queen Mary Hospital, Hong KongUniversity, hospital or other
- Study start
- 18 Sep 2023 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 31 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This study is a double-blind randomised controlled trial on NAC as an adjunctive treatment for acute COPD exacerbation. The randomization will be done via computer software with half of the patients randomized to received oral NAC (600 mg twice daily) and half receive placebo, with randomization ratio being 1 to 1. Patients in the two randomised group will be asked to participate in the study for a maximum of 1 week.
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine | Experimental | Drug: N-acetylcysteine |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 40 years or above, either male or female.
- Patients who are current or ex-smokers
- Patients with a pre-existing diagnosis of COPD admitted to the general medical and respiratory subspecialty wards for acute COPD exacerbation
- Patients who consent to join this clinical trial
Key exclusion criteria (6 listed)
- Patients who are on long-term NAC treatment
- Patients who are not able to take NAC including drug allergy
- Patients with other co-existing respiratory diseases including but not limited to asthma, interstitial lung diseases, and bronchiectasis
- Patients on non-invasive or invasive mechanical ventilation where oral medication is not allowed
- Patients on long term macrolide treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteinePatients 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. | Drug | N-acetylcysteine |
| PlaceboPatients 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. | Drug | Placebo |
Primary outcome
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.
14 secondary outcomes
The change in PaO2/FiO2 ratio
Time frame: from baseline to day 7
The change in sputum volume
Time frame: from baseline to day 7
The Change in COPD Assessment Test (CAT) score
Time frame: from baseline to day 7
The Change in Leicester cough questionnaire (LCQ) score
Time frame: 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 dyspnoea on the modified Medical Research Council (mMRC) Dyspnoea Scale
Time frame: from baseline to day 7
The change in FEV1
Time frame: from baseline to day 7
The change in end tidal CO2
Time frame: from baseline to day 7
The change in SaO2
Time frame: from baseline to day 7
The change in PaCO2
Time frame: from baseline to day 7
The time to wean off supplemental oxygen
Time frame: from baseline to day 7
The length of stay
Time frame: from baseline to day 7
The blood inflammatory markers
Time frame: from baseline to day 7
The 28- and 90-day mortality
Time frame: from baseline to 28- and 90-day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 39108325Kwok WC, Chan SKS, Chiang KY, Ho CMJ. A double-blind randomized controlled trial of N-acetylcysteine (NAC) for the treatment of acute exacerbation of chronic obstructive pulmonary disease. Respirol Case Rep. 2024 Aug 6;12(8):e01449. doi: 10.1002/rcr2.1449. eCollection 2024 Aug.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wang Chun Kwok, MBBS principal investigator
Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing N-acetylcysteine in people with Chronic Obstructive Pulmonary Disease, run by Queen Mary Hospital, Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wang Chun Kwok, MBBS (+852 2255 5336, herbert728@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in mean PaO2 and the change of PaO2 (time frame: day 7; from day 0 to day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05706402, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.