Clinical trial NCT03304028: MUCOviscidose EXacerbation Outils Connectés Education Thérapeutique
Official title: Use of Home-based Connected Devices to Early Detect and Treat Pulmonary Exacerbations: Feasibility and Clinical Validity in CF Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cystic Fibrosis
Keywords: Connected Devices
Pulmonary Exacerbations
Cumulative Sum (CUSUM) Chart
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: Fondation pour la Recherche Médicale
name: Vertex Pharmaceuticals Incorporated
name: Fondation Ildys
First posted: 2017-10-06
Enrollment: 36
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, longitudinal pilot study on cohort, in 3 phases
Primary purpose: PREVENTION

Brief summary: Early detection of pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) patients is important to quickly trigger treatment and reduce respiratory damage. The investigators hypothesize that using home-based connected devices (CDs) in educated patients applying Cumulative sum charts (CUSUM) to monitor physiological parameters (PP) and patients' perception reported (PRP), will allow early detection of PEx.

Objective: to study clinical validity of using CDs and evaluate adherence and satisfaction in CF patients and teams

Design: 3 phase multicenter study in 36 CF patients aged \>=12 years. Phase 1, patients are equipped during 3 months with CDs. PP and PRP to estimate CUSUM parameters are collected. In phase 2, patient's personalized educational plan to manage alerts is built. In phase 3, PP and PRP are collected during 12 months. Clinical validity, change in patients clinical data, quality of Life/Anxiety-Depression/Satisfaction, patients and teams' acceptance and adherence are assessed.

Detailed description: BACKGROUND

Pulmonary exacerbations (PEx) are the major cause of lung function decline in Cystic Fibrosis (CF) patients leading to respiratory failure. Identifying warning signs of PEx is a priority to trigger early treatment and reduce respiratory damage. Some authors tried to define scores based on symptoms to standardize treatment. However, lack of consensus led the Euro-Care-CF-Working-Group to recommend the use of medical antibiotic treatment decision (or treatment modification) associated with PEx-like symptoms as best definition of PEx for clinical trials.

A DELPHI study identified 10 signs frequently perceived by patients and 10 most often cited indicators by caregivers. Two studies have shown that a combination of physiological parameters (PP) and patient reported perceptions (PRP) such as weight loss, decreased spirometry , increased cough or increased sputum production reported daily, help diagnose PEx episodes and trigger early treatment. Clinical observations show that changes in PP and PRP related to PEx differ according to age and degree of lung function impairment. Currently, patients with CF do not routinely monitor their lung function at home, nor do they objectively track PP or PRP. Consequently, CF PEx can be diagnosed late when symptoms progress, in which they seek medical care. Thus, development of an effective approach that helps to monitor daily indicators of PEx to early identification and treatment is important.

* Home monitoring of PEx symptoms Several studies have been conducted with daily monitoring of PEx symptoms. Most of these studies monitored one or two respiratory parameters with data transmission to the medical staff who decide what course of action to take. In addition, these studies used for each parameter the same alert limit for all patients, as it is known that patients with CF have different thresholds of these indicators,some may present more frequently than others.
* CUSUM to monitor indicators of pulmonary exacerbation The use of statistical process control (SPC) shows promise for monitoring indicators of CF PEx and rapidly detecting unwanted changes in these indicators. SPC uses rigorous time-series analysis methods, with results reported as a graph of changes in indicators over time\[9\]. Moreover, SPC can help to determine whether these changes are real (related to a causative factor) or merely a manifestation of natural variability. Among SPC, cumulative sum (CUSUM) chart has been found effective for measuring and monitoring healthcare outcome. It detects changes rapidly, and can identify small shifts. Connected devices software programming integrating CUSUM alert limits can help to determine whether the changes in PP and PRT are due to real PEx episode.

STUDY HYPOTHESIS The investigators hypothesize that using home-based CDs applying CUSUM with patient's personalized alert limits to monitor physiological data and PRP combined with patient education allows early detection of PEx. Studying alerts can help clinicians to develop a patient's personalized educational plan allowing patients better management of PEx including ability to make informed choices. This study aims to assess clinical validity of using different CDs, acceptance and adherence of patients of data collection of physiological data and PRPs, and acceptance by the clinical teams of this process of care. It will lead a larger trial aiming to evaluate efficacy of this process of care on patient's clinical outcomes.

DESIGN

Design: A 3 phase multi-center prospective longitudinal pilot study will be conducted.

- Phase 1- Baseline data collection Clinic staff will email all patients or parents (pediatric settings) to introduce the study. A qualitative interview with 10 patients who declined to participate in the study will be conducted to identify the reason of refusal.

M0: Inclusion visit: the inclusion will be proposed at a follow-up visit by the child's or adult's referring doctor. A written informed consent form will be obtained from all adults or both parents of children.

Quality of Life and Anxiety-Depression will be collected using the HADS and CFQ-R scale Each included patient will be equipped with CDs-spirometer, oxymeter, scale and watch During 3 months: Baseline data of 14 warning indicators of Pex will be collected during 3 non consecutive days a week using the CDs.

Number and time of acute PEx, FEV1, weight, respiratory symptoms and antibiotic treatments prescribed will be collected at the end of the period from the medical patient chart in the CF centre.

* Phase 2- statistical analysis and patient education Statistical analysis of the data collected in phase 1 will take place to calculate the CUSUM parameters. Alert parameters for each patient are then fixed. An educational visit will be scheduled with patients
* Phase 3- CDs use and personalized care PP and PRP will be continuously collected during 12 months using CDs. If alerts occur, patients will be informed by email or SMS, with data transmission to the medical team who will not interfere. Patients should apply the shared action plan they learned. Quality of Life and Anxiety-Depression will be collected using the HADS and CFQ-R scale. Number and time of acute PEx, FEV1, weight, respiratory symptoms and antibiotic treatments prescribed during the period will be collected at the end of the period from the medical patient chart in the CF centre.

At the end of Phase 3: Semi-structured interviews will be completed with the 30 patients/parents and 5 medical teams to explore confidence on the CDs, impact on the doctor-patient relationship, change in the workload of medical team...etc.

EXPECTED RESULTS

The investigators expect a better quality of life for patients, and that their anxiety-depression has not increased or rather decreased. For the clinical teams, the investigators aim to demonstrate that the use of CDs at home by educated patients is acceptable in their daily workload, and satisfying regarding the application of the shared action plan by the patient. Unlike other studies, patients are empowered to initiate actions when alerted by variations of the parameters. If they don't follow the action plan decided with the clinical teams, the treatment of PEx might not be earlier than if they didn't use CDs. In that case, a discussion with the clinicians may lead to the alternative process in which the alerts are used by the clinical teams to drive the actions for the patient. Interestingly, this alternative is possible because the alerts are simultaneously transmitted to the patient and to the team. The leader in the process may even change at some critical periods when the patient is in bad condition or depressed.

Qualitative analysis will provide knowledge on benefits and pitfalls to improve confidence in the use of CDS at home from the patients and the clinical teams, improve the patient-team partnership and, decrease stress and anxiety about pulmonary exacerbation treatment. This study will lead to further plan a larger trial aiming to evaluate efficacy of this process of care on patients' clinical outcomes

Scientific innovation The use of home based CD is rapidly growing and their contribution to the diagnosis of Pex in CF patients deserves to be fully evaluated. The use of CUSUM is particularly promising for monitoring indicators of CF PEx. Because CUSUM chart detects rapidly changes in these indicators and can identify small persistent shifts, it can help to trigger early treatment and reduce respiratory damages.

Furthermore, this is the first study which uses a combination of numerous CDs to evaluate several warning indicators of PEx. In addition, putting patients at the center of their health care and giving them more autonomy (empowerment) is innovative in this type of study and can improve both detection and management of their PEx episodes.

Eligibility criteria: Inclusion Criteria:

* 12 years and over
* Cystic fibrosis confirmed by sweat test or genetic
* Able to understand and respect the protocol and its requirements
* Who signed the consent prior to any other procedure protocolFollowed in the same CF center during the study
* In clinically stable condition - no pulmonary exacerbation requiring intravenous antibiotics - in the previous 4 weeks)
* Prescribed at least one pulmonary medication (eg, inhaled mucolytic, inhaled or oral antibiotic therapy, hypertonic saline)
* Not undergone solid organ transplants
* With smartphone, computer or tablet connected to wifi access

Exclusion Criteria:

* Patient undergoing solid organ transplant
* Pregnancy or planned pregnancy during the period of the study
* Patient on exclusion period because of other clinical research esearch
* Patients who don't use connected devices during the 3 first months will be excluded from the study.

Primary outcomes:
measure: Exacerbations (ExR) concordance
timeFrame: 2 Years
Secondary outcomes:
measure: Hospital Anxiety and Depression scale (HADS)
timeFrame: Inclusion ; month 3 ; month 10 ; month 22
measure: Cystic Fibrosis Questionnaire-Revised (CFQ-R)
timeFrame: Inclusion ; month 3 ; month 10 ; month 22
measure: Medical data : FEV1
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Medical data: Weight
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Medical data: Height
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Medical data: Heart rate
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Medical data: Oxygen saturation
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : FEV1
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : Heart rate
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : Oxygen saturation
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : Weight
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : Duration of sleep
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Physiological parameters with connected devices (PP) : Physical activity
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Perceptions identified by patients (PRP)
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Traitements Number
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Traitements Duration
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Respiratory symptoms
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Exacerbations Number
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Exacerbations Timing
timeFrame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
measure: Patients and professionals interviews
timeFrame: 2 Years
Other outcomes:
Locations:
city: Lille
country: France
facility: CF adults center - Hopital Albert Calmette
city: Nantes
country: France
facility: CF adults center - Institut du Thorax
city: Nantes
country: France
facility: CF pediatrics center - Hopital Mère-Enfant
city: Paris
country: France
facility: CF pediatrics center - Hopital Robert Debré
city: Reims
country: France
facility: CF adults and pediatrics center - American Memorial Hospital
city: Roscoff
country: France
facility: CF adults and pediatrics center- Perharidy
city: Versailles
country: France
facility: CF pediatrics center - Hopital André Mignot
Study officials:
affiliation: Fondation Ildys
name: Gilles RAULT, Ph
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morsa M, Perrin A, David V, Rault G, Le Roux E, Alberti C, Gagnayre R, Pougheon Bertrand D. Use of Home-Based Connected Devices in Patients With Cystic Fibrosis for the Early Detection and Treatment of Pulmonary Exacerbations: Protocol for a Qualitative Study. JMIR Res Protoc. 2021 Aug 18;10(8):e14552. doi: 10.2196/14552.