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Trial registered on ANZCTR


Registration number
ACTRN12613000458730
Ethics application status
Approved
Date submitted
1/04/2013
Date registered
22/04/2013
Date last updated
22/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Paroxetine for Anxiety in Patients with Chronic Obstructive Pulmonary Disease(emphysema).
Scientific title
Paroxetine for Anxiety in Patients with Chronic Obstructive Pulmonary Disease (COPD).
Secondary ID [1] 282227 0
Nil Known
Universal Trial Number (UTN)
U1111-1141-2980
Trial acronym
PAC Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anxiety 288741 0
COPD 288742 0
Condition category
Condition code
Mental Health 289098 289098 0 0
Anxiety
Respiratory 289099 289099 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Paroxetine 20 mgs daily as oral capsule for 4 months. Adherence and side efects will be monitered by weekly phone calls for first 4 weeks. At the end of 4 months participants will also be asked to return any capsules if remaining to assess overall adherence.
Intervention code [1] 286837 0
Treatment: Drugs
Comparator / control treatment
Identical placebo pill (sugar pill) as oral capsule for 4 months
Control group
Placebo

Outcomes
Primary outcome [1] 289207 0
Anxiety as measured by Beck Anxiety Inventory (mean difference)
Timepoint [1] 289207 0
4 months and 12 months.
Secondary outcome [1] 302033 0
Depression as measured by beck Depression inventory (mean difference)
Timepoint [1] 302033 0
4 months and 12 months.
Secondary outcome [2] 302034 0
Quality of Life as assessed by Chronic Respiratory Questionnaire (CRQ) (mean difference)
Timepoint [2] 302034 0
4 months and 12 months.
Secondary outcome [3] 302035 0
Exercise capacity as measured by 6MWD in meters (mean difference).
Timepoint [3] 302035 0
4 months and 12 months.
Secondary outcome [4] 302036 0
Dyspnea as assessed by MMRC dyspnea scale (mean difference as compared with placebo)
Timepoint [4] 302036 0
4 months and 12 months.
Secondary outcome [5] 302037 0
Hospital bed utilization/health economics analysis
Timepoint [5] 302037 0
4 months and 12 months.
Secondary outcome [6] 302038 0
Lung Function as measured by FEV1
Timepoint [6] 302038 0
4 months and 12 months.
Secondary outcome [7] 302039 0
Adverse events will be monitered by weekly phone calls for first four weeks and will also be documented at 4 months visit. Patients will also be advised to report to the investigators of any side effects that they will experience other than these followup calls/visits. Coomon side effects can be:
Central nervous system: Somnolence , insomnia , headache, dizziness.
Endocrine & metabolic: decreased Libido.
Gastrointestinal: Nausea , xerostomia , constipation , diarrhea.
Genitourinary: Ejaculatory disturbances.
Neuromuscular & skeletal: Weakness , tremor Cardiovascular: Chest pain , palpitations.
Dermatologic: Rash.
Ocular: Blurred vision
Miscellaneous: Diaphoresis.
Timepoint [7] 302039 0
week 1,2,3 &4.
4months and 12 months.
Secondary outcome [8] 302245 0
Smoking dependence as measured by exhaled carbon monooxide.
Timepoint [8] 302245 0
4 months and 12 months.
Secondary outcome [9] 302246 0
Prediction of COPD related mortality as assessed by using BODE index.
BODE: B= BMI in Kgms/m2; O= Obstruction as measured by spirometry in FEV1. ; D= dyspnea as measured by MMRC and E= exercise capacity as measured using 6MWT.
Timepoint [9] 302246 0
4 months and 12 months.

Eligibility
Key inclusion criteria
Patients with:
COPD, as confirmed by lung function testing ie FEV1/FVC <0.70, and
Anxiety symptoms with Beck Anxiety Inventory (BAI) score of >15.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe cognitive impairment.
Terminal cancer.
Pregnancy and lactation.
Unstable psychiatric condition like schizephrenia or active suicidal ideation.
Current use of MAOinhibitors.
Intolerance or allergy to SSRIs.
Prolonged QT interval on ECG.
Current acute exacerbation of COPD
Current use of regular antianxiety and antidepressant medications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Based on our primary outcome of anxiety as measured by using Beck Anxiety Inventory (BAI), a sample size of 56 in each group will have 80% power to detect a difference in means of 5.0 assuming that the common standard deviation is 9.3 using a two group t-test with a 0.05 two-sided significance level. Since outcome is being measured at baseline and post-intervention, use baseline adjustment reduces the required sample size. Namely, the required sample size is (1 – r2) n where r is the correlation between baseline and post-intervention readings, and n is the above sample size from a simple t-test. Assuming r = 0.5, then the required sample size per group is 0.75n, ie 42 per group. Allowing for 15% withdrawal, we therefore aim to recruit 50 patients per treatment arm.

Descriptive statistics, response rates and follow-up prevalence of anxiety will be calculated. The primary hypothesis comparing prevalence of anxiety after 4 months by treatment arm will be undertaken using a two-sided chi-squared test. A log binomial GLM model will be used to explore changes in anxiety levels over time as part of secondary analyses. The results presented will follow the Consort Statement Performa, and will be on an intention to treat basis. The statistical package STATA 11 and SPSS 19, with intention to treat, will be used for all analyses. Imbalances in all outcome measures at baseline will be controlled using linier regression modeling

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/05/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 824 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [2] 825 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [3] 826 0
Repatriation Hospital - Daw Park
Recruitment hospital [4] 888 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 889 0
Flinders Medical Centre - Bedford Park

Funding & Sponsors
Funding source category [1] 286985 0
Hospital
Name [1] 286985 0
Department of Respiratory Medicine, The Queen Elizabeth Hospital, (TQEH) South Australia, Australia.
Country [1] 286985 0
Australia
Primary sponsor type
Hospital
Name
Department of Respiratory Medicine, TQEH
Address
4A, TQEH
28 Woodville Road,
Woodville South, SA 5011
Country
Australia
Secondary sponsor category [1] 285773 0
None
Name [1] 285773 0
Address [1] 285773 0
Country [1] 285773 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289034 0
HUMAN RESEARCH ETHICS COMMITTEE (TQEH/LMH/MH)
Ethics committee address [1] 289034 0
DX 465101
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011
Ethics committee country [1] 289034 0
Australia
Date submitted for ethics approval [1] 289034 0
18/01/2012
Approval date [1] 289034 0
30/04/2012
Ethics approval number [1] 289034 0
2012012

Summary
Brief summary
An association between increased dyspnoea scores, mood disorders and anxiety levels in patients with COPD has been well established. On a neurochemical level, this association has been further explained in rat models showing that prolonged hypoxia affects the areas of the brain involved in mood control. The understanding of mechanisms of mood control by antidepressants has evolved over time. The strong antidepressant activity of Tricyclic Antidepressants (TCAs) has supported the role of both norepinephrine and serotonin (5-HT) in mood disorders. The next generation of antidepressants included the Selective Serotonin Reuptake Inhibitos (SSRIs), further supporting the role of serotonin. Furthermore, antidepressants have been hypothesised to work in COPD patients by decreasing autonomic over-activity, or detaching excessive distress associated with COPD, thus enabling patients to better endure increased physical activity and physiological changes.

Hence, our hypothesis is that subjects recruited from public hospitals with COPD and clinically significant depression and/or anxiety that are given paroxetine 20 mgs daily for 4 months will:

(Hypothesis 1: principle hypothesis): have a significant reduction in their anxiety symptoms as compared with the placebo at 4 months follow-up, and;

(Hypothesis 2): these improved levels of anxiety will be associated with:
improved quality of life and exercise capacity, and

(Hypothesis 3): these improved levels of anxiety will be associated with:
a.) a reduction in hospital bed utilisation, and;
b.) a reduction in health care costs in relation to existing practice in long term (12 months)
Trial website
Trial related presentations / publications
Public notes
Primary outcome assessments will occur at 4 months. However in order to assess the longterm effects all the outcomes will be reassessed at 12 months.

Contacts
Principal investigator
Name 38902 0
Dr Zafar Ahmad Usmani
Address 38902 0
4A, Department of Respiratory Medicine,
The Queen Elizabeth Hospital (TQEH).
28 Woodville Road,
Woodville South, SA, Australia, 5011
Country 38902 0
Australia
Phone 38902 0
61-0438360714
Fax 38902 0
61882226041
Email 38902 0
[email protected]
Contact person for public queries
Name 38903 0
Zafar Ahmad Usmani
Address 38903 0
4A, Department of Respiratory Medicine,
TQEH.
28 Woodville Road,
Woodville South, SA, Australia, 5011
Country 38903 0
Australia
Phone 38903 0
61-0438360714
Fax 38903 0
61882226041
Email 38903 0
[email protected]
Contact person for scientific queries
Name 38904 0
Zafar Ahmad Usmani
Address 38904 0
4A, Department of Respiratory Medicine,
TQEH.
28 Woodville Road,
Woodville South, SA, Australia, 5011
Country 38904 0
Australia
Phone 38904 0
61-0438360714
Fax 38904 0
Email 38904 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA randomized placebo-controlled trial of paroxetine for the management of anxiety in chronic obstructive pulmonary disease (PAC study).2018https://dx.doi.org/10.2147/JMDH.S166022
N.B. These documents automatically identified may not have been verified by the study sponsor.