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Trial registered on ANZCTR


Registration number
ACTRN12623000152628
Ethics application status
Approved
Date submitted
28/01/2023
Date registered
16/02/2023
Date last updated
16/02/2023
Date data sharing statement initially provided
16/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Acceptability, feasibility and impacts of remote symptom monitoring and automated treatment plans in children with Cystic Fibrosis (CF) on highly effective modulators: a pilot randomised controlled trial.
Scientific title
Acceptability, feasibility and impacts of remote symptom monitoring and automated treatment plans in children with Cystic Fibrosis (CF) on highly effective modulators: a pilot randomised controlled trial.
Secondary ID [1] 308834 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis 328793 0
Condition category
Condition code
Respiratory 325803 325803 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 325873 325873 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Rationale and background:
We are interested in investigating the feasibility, acceptability and effect of a new remote symptom monitoring an automated treatment plan model of care in children with Cystic Fibrosis (CF) on highly effective modulators. There is current evidence pointing to the feasibility of remote symptom monitoring in people with CF, however all were performed prior to widespread access to highly effective modulators and all required the involvement of the CF multidisciplinary team (MDT) to direct treatment recommendations. This study will generate new evidence relating to the use of remote symptom monitoring and automated treatment plans in children with CF on highly effective modulators.

Trial design:
This will be a pilot randomised, non-blinded, single center trial in children with CF attending the Royal Children’s Hospital (RCH) on highly effective modulators. The study will compare usual care (control arm) to an intervention arm, with the intervention being the new remote symptom monitoring and automated treatment plan model of care. The new model of care will be housed in the electronic medical record (EMR) used by RCH.

The trial will use the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS), a validated tool for detecting pulmonary exacerbations in people with CF for the symptom monitoring.

Description of intervention:
Participants randomised to the intervention arm will receive onboarding material detailing instructions of how to access and use the remote monitoring system via the RCH portal.

Participants will be asked to complete the CFRSD-CRISS in two ways:
1. Baseline symptom survey (copy of CFRSD-CRISS can be found in supporting documents - "Baseline and symptom survey") (3 minutes to complete)

Participants will be prompted to complete survey by a push notification sent to their mobile phone and built into the EMR at the:
o Commencement of the trial;
o Each month post commencement of the trial; and
o After each exacerbation is detected.

2. Twice weekly symptom survey (copy of CFRSD-CRISS can be found in supporting documents - "Baseline and symptom survey") (3 minutes to complete)

Participants will be prompted to complete a survey by a push notification sent to their mobile phone and built into EMR twice a week. Monitoring of survey completion will occur by running reports through the EMR. As this pilot is assessing feasibility limited prompting of families to complete surveys will occur.

A score is assigned to each survey field. Every symptom-monitoring questionnaire completed by the patient or patient’s family is compared to their last known baseline questionnaire.
If the frequency or severity of two or more symptoms have worsened compared to baseline, the Exacerbation Pathway is triggered.
If the system detects an exacerbation, it will send an automated treatment plan out to the patient and their caregiver including:
• Directions to commence a specific antibiotic
• Directions to change/or increase airway clearance and inhalation therapy.
Information regarding antibiotic, airway clearance and inhalation therapy prescription will be extracted from the participant’s EMR file.

At this time participants will be asked to complete their symptom survey on a daily basis.
A message will be sent to the CF team alerting them of the exacerbation and the results of the symptoms survey. The RCH respiratory lab will book a telehealth appointment to perform home lung function to provide further detail of the exacerbation. Lung function will be performed at the start of the exacerbation and at 10-14 days later.

10-14 days after the exacerbation pathway is triggered, the program will assess if symptoms reported in the daily symptom survey have returned to baseline or not.
If the patient symptoms return to (or are better than baseline) on day 10-14:
1. The program re-assigns the non-exacerbation tasks:
a. Monthly baseline questionnaire
b. Symptom-monitoring questionnaire (twice a week).
2. An automated In Basket message will be sent to the CF team notifying them that the exacerbation has ceased.
3. An automated message is sent to notify the participant that symptoms have improved and the exacerbation has ceased, instructing them to cease antibiotics (if not already), return to baseline airway clearance and inhalation therapy and complete their normal twice weekly symptom surveys.

If the patient symptoms do not improve on day 10-14 (Extended Exacerbation):
1. A message will be sent to the CF team prompting for a clinical review via telehealth.
2. A notification will be sent to the participant via the portal notifying them that their symptoms have not become better and expect contact from the treating team in 24 hours.

The RCH EMR team have designed a workflow for the pilot to help assist in ensuring all aspects of care are completed.

Participants randomised to the intervention group will also receive all aspects of usual care in addition to the above information, including quarterly visits to the CF clinic.


Trial delivery and staff:
The intervention will be monitored by an experienced team including CF clinicians all with > 5 years specific CF experience (medical, nursing, physiotherapists and respiratory physiologists) alongside the RCH EMR and digital health team.
One of the aims of the new model of care is to decrease the burden of care of visiting the hospital in person, therefore the majority of clinical reviews and lung function testing will occur via telehealth (which is standard practice for the CF team).

Trial duration:
The trial will run for a 12 month period.
Intervention code [1] 325286 0
Treatment: Other
Intervention code [2] 325361 0
Treatment: Devices
Comparator / control treatment
Participants in the control arm will receive usual care which consists of quarterly CF clinic visits (entailing review of symptoms and exacerbations, performance of lung function, gaining an airway sample and review by the wider CF multidisciplinary team) and more urgent visits triggered by telephone calls from families concerned about their child’s clinical status. This model of care relies on the participant/caregiver contacting the CF team if they notice a change in their symptoms.
Control group
Active

Outcomes
Primary outcome [1] 333652 0
To assess the uptake and feasibility of the remote monitoring and automated treatment plans
a. Total number of symptom surveys completed will be compared to total number of surveys expected and presented as a percentage.

Total number of symptom surveys completed will be compared to total number of surveys expected and presented as a percentage. Survey data will be collected directly from the remote symptom monitoring system housed within electronic medical record
Timepoint [1] 333652 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Primary outcome [2] 333653 0
To assess the impact and acceptability of the remote system monitoring and automated treatment plans on family experience (measured as experience of the program; acceptability of the program) compared to usual care;
a) semi structured interviews will be performed with parents one on one with a member of the research team either in person or via videocall pending the preference of the parent.
Timepoint [2] 333653 0
3 months after randomisation
12 months after randomisation
Primary outcome [3] 333750 0
To assess the uptake and feasibility of the remote monitoring and automated treatment plans:

Number of contacts between CF team and family will be collated and compared between the intervention and control group.

Total number contacts (face to face, telehealth, phone call) will be collected directly from the electronic medical record.
Timepoint [3] 333750 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Secondary outcome [1] 417867 0
1. To understand changes in outcome measures over time between the two groups in children on highly effective modulators
- Number of exacerbations detected
o Total number of exacerbations per year will be calculated in each arm and compared between groups

Total number exacerbations will be collected differently between the two groups.
Intervention: Total number of exacerbations will be collected from the remote symptom monitoring system housed in the EMR

Control: Total number of exacerbations will be collected on a three monthly basis in the form of subjective recall collated in a survey
Timepoint [1] 417867 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Secondary outcome [2] 417868 0
To understand changes in outcome measures over time between the two groups in children on highly effective modulators

Change in lung function (Forced Expiration Volume in first second (FEV1))
o Data will be expressed as litres and percentage predicted. For each individual the FEV1 at study entry will be compared to the FEV1 at study completion, to determine the change in FEV1. This will then be compared between groups.

Lung function will be performed either in person or via telehealth at the convenience of the participant. It will follow standard hospital protocol. The data is stored within the electronic medical record and will be collected directly from there.
Timepoint [2] 417868 0
At point of randomisation
12 months post randomisation
Secondary outcome [3] 418143 0
To understand changes in outcome measures over time between the two groups in children on highly effective modulators

- Number of admissions
o Total number of admissions per year will be calculated in each arm and compared.

Total number of admissions will be collected directly from the electronic medical record.
Timepoint [3] 418143 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Secondary outcome [4] 418144 0
To understand changes in outcome measures over time between the two groups in children on highly effective modulators

- Hospital length of stay
o Total number of hospital days per year will be calculated in each arm and compared between groups.

Total number of hospital days will be collected directly from the electronic medical record.

Total number of hospital days will be collected directly from the electronic medical record.
Timepoint [4] 418144 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Secondary outcome [5] 418145 0
To understand changes in outcome measures over time between the two groups in children on highly effective modulators

- Quality of life using (Cystic Fibrosis Questionnaire-Revised (CFQ-R) & Euro Quality of Life 5 dimension (EQ5D-Y)
o Total score (mean and standard deviation) will be compared between groups.

Both questionnaires will be sent out and collected via REDCap.
Timepoint [5] 418145 0
Immediately post randomisation
12 months post randomisation
Secondary outcome [6] 418146 0
To assess the impact and acceptability of the remote system monitoring and automated treatment plans on CF MDT experience (measured as experience of the program; acceptability of the program) compared to usual care;

Semi structured interviews will be performed with members of the CF MDT in a focus group with one member of the research team. The focus group will either be performed in person or via videocall pending preference of the team.
Timepoint [6] 418146 0
3 months post randomisation
12 months post randomisation
Secondary outcome [7] 418147 0
To assess the cost-effectiveness of the remote monitoring and automated treatment plans compared to usual care by undertaking a health economic evaluation from both the perspective of the healthcare system and caregivers.

a. The cost of the new model will be estimated from the study protocol and budgets.
Timepoint [7] 418147 0
12 months post randomisation
Secondary outcome [8] 418148 0
To assess the cost-effectiveness of the remote monitoring and automated treatment plans compared to usual care by undertaking a health economic evaluation from both the perspective of the healthcare system and caregivers.

b. Difference in the patient’s quality of life (EQ-5D-Y and CFQ-R) will be measured within the trial period for each arm

Both questionnaires will be sent out and collected via REDCap.
Timepoint [8] 418148 0
Immediately post randomisation
12 months post randomisation
Secondary outcome [9] 418149 0
To assess the cost-effectiveness of the remote monitoring and automated treatment plans compared to usual care by undertaking a health economic evaluation from both the perspective of the healthcare system and caregivers.

c. Health service cost from hospital linked data along with patient costs

Health service utilsation will be collected directly from the electronic medical records. Associated costs per hospital contact will be calculated in conjunction with a health economist on the research team.
Timepoint [9] 418149 0
3 months post randomisation
6 months post randomisation
12 months post randomisation
Secondary outcome [10] 418150 0
To assess the cost-effectiveness of the remote monitoring and automated treatment plans compared to usual care by undertaking a health economic evaluation from both the perspective of the healthcare system and caregivers.

d. Cost-effectiveness estimates of a cost per exacerbation avoided for the new model compared with standard care will be generated for the trial period to justify the value of the new model of health monitoring.

Total number exacerbations will be collected differently between the two groups.
Intervention: Total number of exacerbations will be collected from the remote symptom monitoring system housed in the EMR

Control: Total number of exacerbations will be collected on a three monthly basis in the form of subjective recall collated in a survey
Timepoint [10] 418150 0
Immediately post randomisation
12 months post randomisation
Secondary outcome [11] 418449 0
To assess the cost-effectiveness of the remote monitoring and automated treatment plans compared to usual care by undertaking a health economic evaluation from both the perspective of the healthcare system and caregivers.

e. Cost-effectiveness estimates of a cost per Quality Adjusted Life Years for the new model compared with standard care will be generated for the trial period to justify the value of the new model of health monitoring.

Quality Adjusted Life Years will be calculated using data from the EQ5D-Y which will be collected via REDCap.
Timepoint [11] 418449 0
Immediately post randomisation
12 months post intervention
Secondary outcome [12] 418450 0
To assess the uptake and feasibility of the remote monitoring and automated treatment plans:

Total number of tasks completed will be compared to expected number of tasks completed and presented as a percentage

Total number of tasks completed will be compared to total number of tasks expected and presented as a percentage. Task data will be collected directly from the remote symptom monitoring system housed within electronic medical record
Timepoint [12] 418450 0
3 months post randomisation
6 months post randomisation
12 months post randomisation

Eligibility
Key inclusion criteria
- Diagnosis of Cystic Fibrosis
- On a highly effective modulator (either ivacaftor or elexacaftor–tezacaftor–ivacaftor for a minimum of 2 weeks)
- Clinically stable without antibiotic treatment for a pulmonary exacerbation in 2 weeks prior to consent
- Attending RCH CF clinic
- Able to complete home spirometry (standard of care for all children with CF >5 years at RCH CF clinic)
- Sufficient English to complete a survey
- Access to a smart phone to access remote symptom monitoring surveys
Minimum age
5 Years
Maximum age
19 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants not signed up or not willing to sign up to the RCH Portal (note that 80% of RCH CF patients are already signed up to the portal)
- Participants who do not have access to a smartphone or computer on a daily basis
- Participants who do not have access to a home spirometer for lung function purposes
- Participants will be excluded from the study for technological access reasons such as lack of access to the RCH Portal and IT equipment as this is the basis of the intervention.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation will occur after consent is signed and will be performed by a person independent to the study. The schedule will be held by an independent person, and allocation will not be revealed prematurely to the research team. Because of these procedures, the research team will be unable to predict which group the participant will be allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A stratified randomization will be employed with the goal of ensuring balance between study arms by risk category employed by the RCH CF team. The randomisation schedule will be created by computer-generated random numbers, before the first participant has been recruited. The participant cohort will be stratified by child risk category (2 levels of category: 1 Very high risk & high risk and 2 Medium risk & low risk). Within each strata, permuted block randomisation will be used to ensure balance between the intervention and control group. A randomly generated sequence of block sizes containing 2, 4, or 6 participants will be used. This will help ensure balance in numbers between intervention and control groups, prevent potential confounders of risk category type impacting the measurement of outcomes, and prevent any predictability in intervention allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size:
Although this is a randomised controlled trial it is a pilot and currently there is no known sample size in the literature relating to a pilot trial. However, we will aim to include a minimum of 30 participants in the study in line with other pilot trials conducted by trial investigator Hiscock. We believe this will give us sufficient data on the feasibility and acceptability of the new model of care and potential effectiveness. If the intervention is feasible and acceptable the outcome data, which can be collected with minimal burden on participants and resources, will be crucial to inform sample size calculations for fully powered RCTs.

Quantitative analysis:
Statistical analysis will be performed utilizing Statistical Package for the Social Sciences (SPSS). Descriptive statistics will be presented as mean (standard deviation, SD) or median (interquartile range, IQR). Categorical variables will be reported descriptively using frequency (n) and proportion (%).
Comparison between groups will occur using t-tests or Chi squared test (or non-parametric alternatives as required)
Cost analysis - Sensitivity analyses will be used to explore the variation in data. Wide cost confidence intervals are expected with a pilot study. The data collection will however inform acceptability and feasibility of economic data and contribute to the case or otherwise for a full trial

Qualitative analysis:
Semi structured interview transcripts will be imported into NViVo for analysis. Inductive thematic analysis will be used, where initially text will be coded relating to factors influencing family and CF MDT perceptions and attitudes to the new model of care. Themes will be developed relating to codes, emerging inductively from the data. An audit trail will be produced to keep a record of coding decisions. De-identified quotations will be used from the transcripts to illustrate important aspects of parent’s and the MDT staff attitudes to the new model of care versus usual care.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/02/2023
Actual
Date of last participant enrolment
Anticipated
10/04/2023
Actual
Date of last data collection
Anticipated
13/05/2024
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23884 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 39348 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 313058 0
Hospital
Name [1] 313058 0
Royal Children's Hospital
Country [1] 313058 0
Australia
Primary sponsor type
Hospital
Name
Royal Children's Hospital
Address
50 Flemington Road Parkville, 3052 Victoria
Country
Australia
Secondary sponsor category [1] 314746 0
Other
Name [1] 314746 0
Murdoch Children's Research Instituite
Address [1] 314746 0
48 Flemington Road, Parkville Victoria 3052
Country [1] 314746 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312310 0
The Royal Children’s Hospital Melbourne Human Research Ethics Committee (HREC)
Ethics committee address [1] 312310 0
Ethics committee country [1] 312310 0
Australia
Date submitted for ethics approval [1] 312310 0
27/10/2022
Approval date [1] 312310 0
17/01/2023
Ethics approval number [1] 312310 0
91117/RCHM-2022

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124198 0
Miss Jennifer Corda
Address 124198 0
Royal Children's Hospital
50 Flemington Road Parkville Victoria 3052
Country 124198 0
Australia
Phone 124198 0
+61 3 9345 9300
Fax 124198 0
Email 124198 0
[email protected]
Contact person for public queries
Name 124199 0
Jennifer Corda
Address 124199 0
Royal Children's Hospital
50 Flemington Road Parkville Victoria 3052
Country 124199 0
Australia
Phone 124199 0
+61 3 9345 9300
Fax 124199 0
Email 124199 0
[email protected]
Contact person for scientific queries
Name 124200 0
Jennifer Corda
Address 124200 0
Royal Children's Hospital
50 Flemington Road Parkville Victoria 3052
Country 124200 0
Australia
Phone 124200 0
+61 3 9345 9300
Fax 124200 0
Email 124200 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No, as this is a pilot study using a hospital specific electronic medical record function the results would not be relevant to pooling with other studies


What supporting documents are/will be available?




Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.