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Trial registered on ANZCTR


Registration number
ACTRN12612000807853
Ethics application status
Approved
Date submitted
26/07/2012
Date registered
2/08/2012
Date last updated
2/08/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Phenotype based management of severe persistent asthma
Scientific title
Multidisciplinary phenotype based management for people with severe persistent asthma compared to usual care and its impact on health related quality of life.
Secondary ID [1] 280679 0
Nil
Universal Trial Number (UTN)
Trial acronym
SAIM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe persistent asthma 286707 0
Condition category
Condition code
Respiratory 287003 287003 0 0
Asthma
Inflammatory and Immune System 287004 287004 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the intervention group will undergo a multidimensional assessment and individualised management (MDAIM) which aims to provide evidence based care through a case management approach, to people with severe persistent asthma. Assessment and treatment will be targeted to co-morbidities, inflammatory and other immunological biomarkers through a multidisciplinary case management approach and using inflammometry. The multidimensional assessment will involve 2 baseline assessments each of approximately 2.5 hours duration. The tailored interventions will be standardised according to best available evidence and will include: optimal medical management including tailoring pharmacotherapy according to airway and systemic inflammation and guiding the exacerbation plan, individualised smoking cessation counselling and pharmacotherapy, management of anxiety and depression, management of mucous hypersecretion, exacerbation management, management of dysfunctional breathing, correction of nutritional and metabolic disorders, implementation of domiciliary oxygen, self management education and support, management of airflow obstruction and co-morbidities, correction of adherence, exercise training, treatment of infection, management of dyspnea, symptoms and patient identified problems.
The intervention will be standardised and include 3 key features, a comprehensive assessment to determine the clinical problems and a tailored care plan and follow up. Whilst each participants care plan will differ the recommended interventions will be standardised. The frequency of clinical contact a participant will have may differ depending on the intervention received, however may range between once weekly to once monthly. Participants may be seen by more than one clinician in one week, however the appointments will occur in the same day, one after the other for participant convenience. The duration of the study will be 16 weeks and therefore intervention duration will be 16 weeks.
Intervention code [1] 285087 0
Treatment: Drugs
Intervention code [2] 285088 0
Lifestyle
Intervention code [3] 285388 0
Treatment: Other
Comparator / control treatment
Following the baseline visit the asthma usual care control group will be treated according to best available evidence in the John Hunter Hospital severe asthma clinic. Usual care will be delivered in the severe asthma clinic which will include medical assessment by a respiratory physician. The participant’s usual specialist physician will provide a medical assessment, a review of co-morbidities, an assessment of lung function and oxygen saturation by spirometry and pulse oximetry, and a diagnosis. The treating physician will schedule follow up appointments as they deem appropriate. Patient will also be reviewed by a nurse specialist to assess and address asthma management knowledge and skills.
Control group
Active

Outcomes
Primary outcome [1] 287336 0
Health related quality of life as measured by the Juniper Asthma Quality of Life Questionnaire.
Timepoint [1] 287336 0
At baseline and week 16 following completion of study.
Secondary outcome [1] 297929 0
Systemic inflammatory markers (CRP, IL-6) measured by ELISA
Timepoint [1] 297929 0
Baseline and week 16
Secondary outcome [2] 297930 0
Airway inflammation measured by sputum cell counts
Timepoint [2] 297930 0
Baseline and week 16
Secondary outcome [3] 297931 0
Asthma control measured by Juniper Asthma Control Questionnaire
Timepoint [3] 297931 0
Baseline and week 16
Secondary outcome [4] 297932 0
Lung function measured by spirometry (Medgraphics CPFS/D instrumentation, Minnesota, USA)
Timepoint [4] 297932 0
Baseline and week 16
Secondary outcome [5] 297933 0
Sputum gene expression (by qPCR) of targets previously associated with severe persistent asthma, including MMP9 and members of the p38 signalling pathway measured by quantitative polymerase chain reaction.
Timepoint [5] 297933 0
Baseline and week 16
Secondary outcome [6] 297934 0
Body composition measured by dual energy xray absorptiometry
Timepoint [6] 297934 0
Baseline and week 16
Secondary outcome [7] 297937 0
Exercise capacity will be assessed using the 6 minute walk test
Timepoint [7] 297937 0
baseline and week 16

Eligibility
Key inclusion criteria
-Diagnosed with severe persistent asthma defined as uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity including impaired lung function) on maximal treatment with inhaled corticosteroid and long-acting Beta2-agonist
-Confirmed variable airflow obstruction at screening visit or documented within the past 10 years
-Bronchodilator response >200ml OR > 12% (post-bronchodilator FEV1 following administration of 400mcg salbutamol, pMDI with spacer; after 10 minutes, or following administration of nebulised ventolin)
-Airway hyperresponsiveness (in response to any standard challenge agent)
-Peak flow variability >12%
-FEV1 variability > 12%
-If not observed, then hypertonic saline challenge at visit 1 (pD15 < 15mL saline).
-Aged >18 years.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Aged < 18 years.
-Treatment with any macrolide or tetracycline 4 weeks prior to screening.
-Treatment with oral corticosteroids 4 weeks prior to screening (unless a low dose is being taken on a long-term basis: 10mg for >3 months)
-Hypersensitivity to macrolides
-Prolonged QTc > 0.44s at screening or during treatment
-Taking medication that will interact with azithromycin in regard to QTc prolongation
-Existing ECG abnormalities that may lead to arrhythmias
-Pregnancy/breast feeding, likely to become pregnant or unwilling to use an additional form of contraception for the first 2 months of treatment if taking the oral contraceptive pill
-Diagnosed with respiratory disease other than severe persistent asthma or bronchiectasis (e.g. active tuberculosis, pulmonary fibrosis) OR diagnosed with coexisting respiratory disease that, at investigator’s discretion, would adversely impact on study conduct.
-Current lung cancer or other blood, lymphatic or solid organ malignancy
-Inability to attend study visits
-Impaired liver function at screening as shown by AST, ALT, alkaline phosphatase or total bilirubin > 1.5 times the upper limit of normal (During treatment if > 2 times the upper limit of normal)
-Impaired renal function at screening as shown by Creatinine Clearance < 30mL/min
-Ocular surgery within 3 months of study entry
-Abdominal, chest or brain surgery within 3 months
-Known cerebral, aortic, or abdominal aneurysm
-Females of child-bearing potential, not using reliable contraception or unwilling to use a second method of contraception during the first 2 months of treatment if taking the oral contraceptive pill
-Participants who have participated in another investigative drug study parallel to, or within 4 weeks of study entry

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)
Concealed random allocation will be employed. In order to ensure optimal matching of groups, the process of minimisation will be used by a third party to randomise participants into two groups.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic (adaptive) random allocation via minimisation will be the method used to generate the sequence in which subjects will be randomised. In order to ensure optimal matching of groups, the process of minimisation will be used by a third party to randomise participants into two groups. They will be randomly assigned to receive MDAIM or usual care. Criteria will be used for stratification will include the baseline eosinophil and neutrophil count in the sputum, and baseline hs-CRP.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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 in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285442 0
University
Name [1] 285442 0
University of Newcastle
Address [1] 285442 0
University Drive
Callaghan NSW 2308
Country [1] 285442 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Locked Bag 1 HRMC
NSW 2310
Country
Australia
Secondary sponsor category [1] 284293 0
University
Name [1] 284293 0
University of Newcastle
Address [1] 284293 0
University Drive
Callaghan NSW 2308
Country [1] 284293 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287456 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 287456 0
Locked Bag 1
New Lambton
NSW 2305
Ethics committee country [1] 287456 0
Australia
Date submitted for ethics approval [1] 287456 0
Approval date [1] 287456 0
06/02/2012
Ethics approval number [1] 287456 0
08/HNE/254

Summary
Brief summary
We have previously demonstrated the effectiveness of a multidimensional assessment and individualised management approach in older people with obstructive airways disease, showing that such a programme leads to significant improvement in health outcomes. The current study aims to continue this new model of management in a different population of people with severe persistent asthma.

People with severe persistent asthma continue to suffer a significantly high burden of disease despite maximal pharmacotherapy. Despite this, few trials seeking to improve management of severe asthma, have been performed. The current study aims to improve the management and outcomes for people severe persistent asthma, with the goal of reducing morbidity, improving health status and informing clinical guidelines.


This study will aim to test a novel model of management in severe asthma using multidimensional assessment and individualised management (MDAIM) including inflammometry and case management. We hypothesize that treatment of severe asthma that is targeted to co-morbidities, inflammatory and other immunological biomarkers delivered using a case management approach will improve severe asthma outcomes specifically asthma control, exacerbations, medication use and health related quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34317 0
Address 34317 0
Country 34317 0
Phone 34317 0
Fax 34317 0
Email 34317 0
Contact person for public queries
Name 17564 0
Penny Baines
Address 17564 0
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights
New Lambton, NSW 2305
Country 17564 0
Australia
Phone 17564 0
+61240420122
Fax 17564 0
+61240420022
Email 17564 0
Penelope.Baines@newcastle.edu.au
Contact person for scientific queries
Name 8492 0
Dr Vanessa McDonald
Address 8492 0
Department of Respiratory and Sleep Medicine
Lot 1 Kookaburra Circuit
New Lambton Heights
New Lambton NSW 2305
Country 8492 0
Australia
Phone 8492 0
+61240420146
Fax 8492 0
+61240420022
Email 8492 0
Vanessa.McDonald@hnehealth.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
No Results