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Trial registered on ANZCTR


Registration number
ACTRN12620000649910
Ethics application status
Approved
Date submitted
28/02/2020
Date registered
4/06/2020
Date last updated
4/06/2020
Date data sharing statement initially provided
4/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The Vietnam COPD Asthma and Prevention of Smoking (VCAPS) 4 Trial
Scientific title
A two-by-two factorial cluster randomised controlled trial evaluating the effectiveness of a stepped treatment algorithm for treating obstructive lung disease, and a behavioural intervention to reduce the prevalence of smoking among smokers in district health facilities in Vietnam.
Secondary ID [1] 300616 0
None
Universal Trial Number (UTN)
Trial acronym
The VCAPS4 Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COPD 316378 0
Asthma 316379 0
Smoking 316380 0
Condition category
Condition code
Respiratory 314636 314636 0 0
Asthma
Respiratory 314637 314637 0 0
Chronic obstructive pulmonary disease
Public Health 314638 314638 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two-by-two factorial cluster randomised trial, and hence there are two independent interventions. Different populations of patients may receive the two interventions. The enrolment period is 12 months for all participants.

The first (Intervention 1) is a stepped chronic respiratory disease intervention, which provides increasing doses of inhaled corticosteroid- long acting beta agonist therapy to patients according to their symptom control. The second (Intervention 2) is a smoking cessation intervention using brief counseling and outpatient smoking cessation counselling using a Quitline.

INTERVENTION 1 (chronic respiratory disease management intervention):
A stepped chronic respiratory disease (CRD) management intervention, comprising three steps.
The active drug is inhaled budesonide-formoterol via Turbuhaler (200-6mcg per dose). All participants begin on Step 1. The treatment step will be individualised: at scheduled reviews, they may be stepped up or down on their therapy according to their symptom control - which is assessed using a standardised questionnaire. Treatment is delivered through the government District Health Clinics, in participating Districts. This treatment replaces usual care.

The steps in the intervention group are:
(a) Step 0: No inhaler therapy.
(b) Step 1 (the initial step, for participants in the intervention group at enrolment): As needed budesonide-formoterol 200-6mcg, with one (1) dose as needed (maximum 12 inhalations in any one day)
(c) Step 2: Budesonide-formoterol 200-6mcg one (1) dose twice daily AND one (1) dose as needed budesonide-formoterol 200-6mcg one (1) when respiratory symptoms are worse than usual (up to 10 additional inhalations per day, i.e. a total maximum of 12 inhalations per day).
(d) Step 3: Refer to specialist care for further assessment, comprising referral for a clinical consultation +/- a telephone consultation with a medical advisor.

Participants will begin at Step 1, at the time of enrolment. During each clinical assessment, participants will be advised to (a) remain on the current step, or (b) step up or (c) step down based upon their symptom control, and whether an exacerbation has occurred.

Patients using an AVERAGE of more than 6 inhalations per day (i.e. less than 20 days between inhaler dispensings) will be identified for clinical review in person or by phone by a medical advisor or study doctor. Medications will be brought by participants to each visit in order to evaluate cumulative treatment. The number of doses used will be determined based upon the counter on the inhaler.

Scheduled reviews for this group will be conducted by a doctor at the health facility. After enrolment, follow-up will occur after 28 days (+/- 7 days), taking approximately 30 minutes. Scheduled follow-up by the health facility doctor lasting 30 minutes will occur at 3, 6, 9 and 12 months.


INTERVENTION 2: A health system smoking cessation (SC) intervention
Individuals allocated to the intervention group will receive brief counselling lasting approximately 5 minutes from healthcare workers at government District Health Clinics, according to the '5As' approach (Ask, Assess, Advise, Assist and Arrange). This treatment replaces usual care.

They will then be referred to an outpatient Smoking Cessation Call Centre, established for this study. The call centre staff will make contact with them by telephone within 24-48 hours after referral. They will then be offered regular follow-up by the Smoking Cessation Call Centre five times in the first 60 days (e.g. days 7, 14, 21, 28, 60, according to patient availability). Each phone call will include brief advice about cessation lasting approximately 15 minutes, based upon the participant's readiness to quit. Participants will be followed 3, 6 and 9 months by telephone by research staff to monitor their smoking status - with no additional delivery of counselling.

After 12 months, participants will be called by research staff and asked about their current smoking status, in a call lasting approximately 10 minutes. Patients who state they are non-smokers will invited to submit a sample of sputum or urine for cotinine testing to confirm the non-smoking status.
Intervention code [1] 316928 0
Treatment: Drugs
Intervention code [2] 316929 0
Lifestyle
Comparator / control treatment
Comparator 1 (chronic respiratory disease management)
Patients eligible to enrol in the control group of the CRD management component of the trial, will receive usual care from healthcare workers at the time of enrolment, without the addition of structured brief advice. 'Usual care' comprises standard medical treatment according to the recommendations of the doctor in the clinic.

Participants will be followed up after 24-48 hours, then 3, 6 and 9 months by research staff by telephone in order to monitor their smoking status. The call will take approximately 10 minutes.

Scheduled follow-up by telephone by research staff lasting 10 minutes will occur at 3, 6, 9 and 12 months.

Comparator 2: Usual care, comprising the standard approach to smoking cessation taken by the treating doctor. No additional outpatient counselling will be provided.

Participants in the comparator arm will be followed up at 3, 6 and 9 months with a telephone call by research staff lasting 10 minutes to monitor their smoking status - with no additional delivery of counselling. After 12 months, participants will be called and asked about their current smoking status by research staff in a call lasting 10 minutes. Patients who state they are non-smokers will invited to submit a sample of sputum or urine for cotinine testing to confirm non-smoking status.
Control group
Active

Outcomes
Primary outcome [1] 323076 0
(Chronic respiratory disease management component): The proportion of individuals with CRD reporting one or more acute exacerbations over the 12 months after enrolment.
Timepoint [1] 323076 0
Within 12 months of enrolment
Primary outcome [2] 323077 0
(Smoking cessation component): The proportion of enrolled smokers who have sustained self-reported and validated smoking cessation twelve months after enrolment.
Timepoint [2] 323077 0
Within 12 months of enrolment.
Secondary outcome [1] 380711 0
One year all-cause mortality, based upon report of household member or health worker or death registry.
Timepoint [1] 380711 0
Within 12 months of enrolment
Secondary outcome [2] 380712 0
The proportion of patients hospitalised with exacerbations during the 12 months following enrolment.
Timepoint [2] 380712 0
This is assessed based upon self-report of patients, reported during follow-up phone calls by research staff after 3, 6, 9 and 12 months. Outcomes are measured within 12 months of enrolment
Secondary outcome [3] 380713 0
The cumulative dose of oral prednisone (or equivalent) in mg taken during the 12 months following enrolment.
Timepoint [3] 380713 0
This will be assessed based upon a treatment diary, whereby patients record the treatments that they take and report them to research staff during scheduled follow-up calls at 3, 6, 9 and 12 months. Outcomes are measured within 12 months of enrolment.
Secondary outcome [4] 380714 0
The proportion of patients that have provided information required to determine the ‘step’ of treatment
Timepoint [4] 380714 0
This will be assessed at 3, 6, 9 and 12 months after enrolment.
Secondary outcome [5] 380715 0
(Smoking cessation component): The proportion of patients self-reporting abstinence from tobacco smoking for at least 30 days prior to 3 months, and prior to 6 months after enrolment.
Timepoint [5] 380715 0
3 months and 6 months after enrolment
Secondary outcome [6] 380716 0
The number of episodes of self-reported presentation to a health facility associated with their own health during the 12-month period after enrolment.
Timepoint [6] 380716 0
12 months after enrolment.
Secondary outcome [7] 380717 0
The difference in readiness to quit smoking between the time of enrolment and 3 months after enrolment. This is assessed using a Stages of Change questionnaire.
Timepoint [7] 380717 0
3 months after enrolment.
Secondary outcome [8] 380718 0
(Both CRD and smoking cessation components): Direct health care utilization, based upon a record of health care episodes and a facility costings survey. This will be based upon participant use of a diary that has been designed specifically for this study.
Timepoint [8] 380718 0
Within 12 months of enrolment.
Secondary outcome [9] 380719 0
(Both CRD and smoking cessation components): Participation rate in the study, based upon an estimate of the average participation during an evaluation period at the start of the study (i.e. the reach of the study).
Timepoint [9] 380719 0
At the time of enrolment.
Secondary outcome [10] 380720 0
(for Chronic Respiratory Disease component): The total number of Grade 3 and 4 adverse events occurring during the follow-up period. Adverse events of special interest will be clinically consistent pneumonia (defined below) or tuberculosis (confirmed based upon smear, culture, PCR or histological testing).
Adverse events will be based upon a clinical history and examination by the doctor at the study site, and laboratory information from the medical record.
Timepoint [10] 380720 0
12 months after the date of enrolment.

Eligibility
Key inclusion criteria
Inclusion criteria for the chronic respiratory disease (CRD) component:
(a) Patients 12 years old and over, presenting to district health facilities; AND:
(b) Presents with at least one of cough, dyspnoea, wheeze or chest tightness, AND
(c) A history of at least one prior episode of respiratory symptoms requiring assessment by a health care facility (clinic, private doctor, pharmacy or hospital) in the past 24 months; AND
(d) Intends to be resident in the Province for the next 12 months
(e) Patients have a method of being contacted during follow-up (e.g. a personal telephone, or telephone of a relative) and
(f) Meets the definition for asthma or COPD, as defined by:
(i) Probable asthma: Score of three or more “YES” responses (out of a total of 9) on the Asthma questionnaire) , OR
(ii) Airflow limitation: either pre-bronchodilator FEV1/FVC ratio < 70% OR (contraindicated or cannot be performed) Peak Expiratory Flow (PEF) <80% predicted at time of presentation;

Inclusion criteria for the smoking cessation (SC) component:
(a) Patients attending the selected health facility AND
(b) Aged 12 years and over; AND
(c) A current smoker (either occasional or daily); AND
(d) Intends to be resident in the Province for the next 12 months; AND
(e) Patients have a method of being contacted during follow-up (e.g. a personal telephone, or telephone of a relative)
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for screening:
(a) Patient cannot provide consent (e.g. due to confusion or dementia)
(b) The patient has respiratory failure (e.g. hypoxaemia requiring supplemental oxygen)
(c) The patient is haemodynamically unstable
(d) Patient currently has active tuberculosis
(e) The patient has a history of bronchiectasis, defined as daily cough and production of purulent sputum for at least 6 months.
(f) Patient has one of the following serious health conditions: aortic aneurysm, current cancer, an illness with a prognosis of <1 year
(g) Allergic to budesonide or formoterol
(h) Patient is currently pregnant
(i) Patients will not be enrolled if a probable alternative diagnosis explains the respiratory symptoms.

Exclusion criteria for the SC component:
(a) Unable to give informed consent, with difficulty with communication or severe mental illness.

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)
This is a cluster randomised controlled trial, where the unit of randomisation is the health facility. All people enrolled at a health facility will be included in the same arm. Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
The populations enrolled in the CRD and SC components of the study will overlap, but not completely. That is, there are two parallel group randomised controlled trials being implemented at the health facility level, with a minority of participants participating in both components.
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The measure of effectiveness will be relative risk, estimated using a log link and binomial error distribution. For the primary analysis, there will be no adjustment for potential confounders. Secondary adjusted analyses will also be performed to account for potential confounding, including age, gender and other factors found to differ between study arms. For binary outcomes, logistic regression will be used to adjust for confounders at the individual and cluster level. We will evaluate the presence of interaction between the smoking cessation intervention and the CRD intervention, using an interaction term in the logistic regression.

Missing data will be addressed using multiple imputation.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22403 0
Viet Nam
State/province [1] 22403 0
Hanoi Capital, Thanh Hoa Province, An Giang Province, Ca Mau Province

Funding & Sponsors
Funding source category [1] 305035 0
Government body
Name [1] 305035 0
National Health and Medical Research Council (NHMRC)
Address [1] 305035 0
16 Marcus Clarke St, Canberra ACT 2601
Country [1] 305035 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
431 Glebe Point Road, Glebe NSW 2037
Country
Australia
Secondary sponsor category [1] 305481 0
None
Name [1] 305481 0
None
Address [1] 305481 0
None
Country [1] 305481 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305430 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 305430 0
Level 3, Administration Building (F23)
University of Sydney NSW 2006
Ethics committee country [1] 305430 0
Australia
Date submitted for ethics approval [1] 305430 0
Approval date [1] 305430 0
11/02/2020
Ethics approval number [1] 305430 0
2019/334
Ethics committee name [2] 305492 0
Ministry of Health Scientific Committee
Ethics committee address [2] 305492 0
138A Giang Vo, Kim Ma, Ba Dinh, Ha Noi, Vietnam
Ethics committee country [2] 305492 0
Viet Nam
Date submitted for ethics approval [2] 305492 0
Approval date [2] 305492 0
27/12/2019
Ethics approval number [2] 305492 0
7752/QD-BYT

Summary
Brief summary
This is a pragmatic 2x2 factorial cluster randomized trial, involving two different components:
(a) for patients with recurrent obstructive lung disease: a chronic respiratory disease component evaluating the effect of a stepped algorithm involving budesonide-formoterol against standard care. This trial will use the single inhaler medication for undifferentiated obstructive lung disease (i.e. asthma or COPD) in order to simplify the algorithm, and therefore optimise the effectiveness of the medication for patients presenting with recurrent respiratory symptoms.
(b) for patients who are current smokers: a smoking cessation component evaluating the effect of a brief counseling intervention (delivered via an outpatient smoking cessation quitline) against standard care (without outpatient counseling).

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100354 0
A/Prof Greg Fox
Address 100354 0
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road, The University of Sydney, NSW Australia 2006
Country 100354 0
Australia
Phone 100354 0
+61 2 9036 3121
Fax 100354 0
Email 100354 0
greg.fox@sydney.edu.au
Contact person for public queries
Name 100355 0
A/Prof Greg Fox
Address 100355 0
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road, The University of Sydney, NSW Australia 2006
Country 100355 0
Australia
Phone 100355 0
+61 2 9036 3121
Fax 100355 0
Email 100355 0
greg.fox@sydney.edu.au
Contact person for scientific queries
Name 100356 0
A/Prof Greg Fox
Address 100356 0
Rm 5216, Level 2 Medical Foundation Building K25
92-94 Parramatta Road, The University of Sydney, NSW Australia 2006
Country 100356 0
Australia
Phone 100356 0
+61 2 9036 3121
Fax 100356 0
Email 100356 0
greg.fox@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Currently undecided.
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 7168 0
Study protocol
Citation [1] 7168 0
Link [1] 7168 0
Email [1] 7168 0
greg.fox@sydney.edu.au
Other [1] 7168 0
Attachment [1] 7168 0
Summary results
No Results