Remote Care in People With Rheumatoid Arthritis (NOR-Flare)

Can Machine Learning and Patient-reported Outcomes be Used in Remote Care in People With Rheumatic Diseases

This study is a 24-months, non-inferiority randomized, controlled trial with two parallel arms to determine if a new follow-up strategy for patients with RA is non-inferior in maintaining comprehensive disease control measured as simultaneous maintenance of structural, functional and clinical treatment target at 2-year follow-up compared to the conventional follow-up regimen with regular hospital visits.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Conventional follow-up; Other: Remote monitoring

Detailed Description

The study will include Norwegian adult males and females with rheumatoid arthritis. Eligible patients that consent to participation will be randomized to two groups:

• Control group: conventional follow-up strategy with blood tests, patient-reported outcomes (PROs), and pre-scheduled visits at the hospital every 6th month.
• Remote monitoring: monthly remote monitoring of PROs and triage of patients using an algorithm will guide healthcare providers in scheduling patients for a video consultation or face-to-face hospital visits.

Participants will be followed for 24 months. Primary outcome is proportionn maintaining comprehensive disease control measured as simultaneous maintenance of structural, functional and clinical treatment target at 2-year follow-up1.

• Structural: Assessed with radiographs of hands and feet according to the van der Heijde modified Sharpe score (subscores for erosions (0-280) and joint space narrowing (0-168)), with a total range of 0-448. Maintenance of structural treatment target is defined as change in total score <1 unit/year (<2 units from inclusion to 2-year follow-up).
• Functional: Measured by Modified Health Assessment Questionnaire (MHAQ) measured on a scale from 0.00 to 3.00, where a change of 0.25 is considered clinical important3. Maintenance of functional treatment target is defined as a worsening <0.25 from inclusion to 2-year follow-up.
• Clinical: Measured by DAS28, categorized into remission (<2.6), low disease activity (2.6 to ≤3.2), moderate disease activity (3.2 to ≤5.1) and high disease activity (>5.1). Maintenance of clinical treatment target is defined disease activity category at 2-year follow-up ≤ baseline category.

We will use a 15% non-inferiority margin.

The study will comprise an internal pilot study the first 6 months for all participants in the intervention group.

The study will also include qualitative research including semi-structured interviews and observations of patients in the intervention group and health professionals involved in the study. The interviews will explore experiences with remote monitoring and video consultations.

• Study Type: Interventional
• Enrollment (Anticipated): 228
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Therese Tveter, PhD; Phone Number: 91115550; Email: AnneTherese.Tveter@diakonsyk.no
• Study Contact Backup: Name: Tuva Moseng, PhD; Phone Number: 47306697; Email: Tuva.Moseng@diakonsyk.no

Study Locations

• Norway
  • Oslo, Norway, 0319
    • Recruiting
    • Diakonhjemmet Hospital
    • Contact: Anne Therese Tveter, PhD; Phone Number: 91115550; Email: a.t.tveter@medisin.uio.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant, non-nursing female ≥18 years of age at screening
• Patients with a diagnosis of RA who fulfil the 2010 ACR/EULAR diagnostic criteria24 (see Appendix 5, 10.4)
• Medical treatment with cs/ts/bDMARDs (incl. prednisolone) considered stable by the healthcare provider the last 6 months
• Low disease activity or remission (CDAI<10 / DAS28<3.2) at inclusion
• <2 swollen joints
• Not deemed inappropriate for remote monitoring by the healthcare provider
• Capable of understanding and signing an informed consent form
• Access to a smartphone or tablet
• Able to speak and understand Norwegian language

Exclusion Criteria:

Medical conditions:

• Major co-morbidities, such as severe malignancies, severe diabetes mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class III or IV), severe respiratory diseases, and/or cirrhosis.
• Indications of active tuberculosis (TB)
• Treated with intravenous DMARD (e.g., rituximab and infliximab)

Diagnostic assessments:

• Abnormal renal function, defined as serum creatinine >142 µmol/L in female and >168 µmol/L in male, or glomerular filtration rate (GFR) <40 mL/min/1.73 m2
• Abnormal liver function (defined as Aspartate Transaminate (AST)/Alanine Transaminase (ALT) >3 x upper normal limit), active or recent hepatitis
• Leukopenia and/or thrombocytopenia

Other:

• Pregnancy and/or breastfeeding (current at screening or planned within the duration of the study)
• Severe psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible.
• Deemed unsuitable for remote monitoring by medical doctor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Conventional follow-up; Conventional follow-up strategy with blood tests and face-to-face visits at the hospital every 6 months	Other: Conventional follow-up; Patients in the conventional/usual care arm will be treated according to current conventional follow-up regimen with PROs, blood tests, and face-to-face visits with an experienced nurse or a rheumatologist every 6 months. They can contact the hospital if they are experience worsening of their disease.; Other Names: Control group
EXPERIMENTAL: Remote monitoring; Monthly remote monitoring of patient-reported outcomes and triage of patients using an algorithm will guide healthcare providers in scheduling patients for a video consultation or face-to-face hospital visits.	Other: Remote monitoring; The patients in the remote monitoring arm will use a web-app (Youwell) for self-reporting patient reported outcomes (PROs) and CRP/ESR, displaying results for PROs over time, and for synchronous (video) or asynchronous (chat) communication with healthcare providers. The patients will receive a SMS reminder for "tasks" (e.g., self-reporting PROs or registering results from blood tests) every month. A study coordinator/nurse will monitor the PROs and blood test (CRP/ESR) results, and respond to chat messages. Based on the algorithm, a triaging functionality in the Youwell platform will aid healthcare providers in highlighting which patients needs attention.; Other Names: Intervention group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion maintaining comprehensive disease control	Comprehensive disease control measured as simultaneous maintenance of structural, functional and clinical treatment target at 2-year follow-up.; Structural: Radiographs of hands and feet according to the van der Heijde modified Sharpe score, with a total range of 0-448. Maintenance of structural treatment target is defined as change in total score <1 unit/year (<2 units from inclusion to 2-year follow-up).; Functional: Modified Health Assessment Questionnaire (MHAQ) measured on a scale from 0.00 to 3.00, where a change of 0.25 is considered clinical important. Maintenance of functional treatment target is defined as a worsening <0.25 from inclusion to 2-year follow-up.; Clinical: DAS28, categorized into remission (<2.6), low disease activity (2.6 to ≤3.2), moderate disease activity (3.2 to ≤5.1) and high disease activity (>5.1). Maintenance of clinical treatment target is defined disease activity category at 2-year follow-up ≤ baseline category.	Baseline and 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in joint damage progression	Joint damage progression from inclusion to 2-year follow-up assessed with radiographs of hands and feet according to the van der Heijde modified Sharpe score (subscores for erosions (0-280) and joint space narrowing (0-168)), with a total range of 0-448. Measured as a continuous variable.	Baseline and 2 years
Self-reported disease activity (intervention group)	Measured with patient global assessment of disease activity (0-10 scale, 0=no disease activity), estimated as change across all timepoints	Monthly until 2 years
Self-reported disease activity (control group)	Measured with patient global assessment of disease activity (0-10 scale, 0=no disease activity), estimated as change across all timepoints	Baseline, 6 months, 12 months, 18 months and 2 years
Health-related quality of life	Measured with EQ5D-5L, 5 questions used to calculate an utility score (0-1, 1= best health), assessed as a total score across all timepoints	Baseline, 6 months, 12 months, 18 months and 2 years
Proportion in remission/low disease activity (CDAI)	Measured with CDAI (patient global assessment of disease activity, number of tender and swollen joints, physician assessment of disease activity). Remission/low disease activity defined as CDAI <10.	Baseline and 2 years
Proportion in remission/low disease activity (DAS28)	Measured with DAS28 (patient global assessment of disease activity, CRP/ESR, number of tender and swollen joints). Remission/low disease activity defined as DAS28 <3.2.	Baseline and 2 years
Disease activity in conjunction with consultation (DAS28)	Measured with DAS28 (patient global assessment of disease activity, CRP/ESR, number of tender and swollen joints). DAS28 score: <2.6= remission; 2.6-<3.2=low disease activity; 3.2 -5.1= moderate disease activity; >5.2= high disease activity	Any consultation from baseline to 2 years
Disease activity in conjunction with consultation (CDAI)	Measured with CDAI (patient global assessment of disease activity, number of tender and swollen joints, physician assessment of disease activity). CDAI score: <=2.8 = remission; >2.8 - <=10 = low disease activity; >10 - <=22 = moderate disease activity; >22 = high disease activity	Any consultation from baseline to 2 years
Health care utilization	Costs related to self-reported healthcare use in primary and secondary health care. Patients will be asked if they have been seeking healthcare (yes/no), if yes, they will be asked to specify type of healthcare use and time used. This information will also be collected from national register data.	Baseline, 6 months, 12 months, 18 months, 2 years
Patient-reported disease flares (intervention group)	Patient-reported experience of a significant worsening of symptoms (reflecting a flare in disease activity), response options: no, yes, uncertain. If yes or uncertain, they will be asked which date the flare occurred and the number of days it lasted.	Every month until 2 years
Patient-reported disease flares (control group)	Patient-reported experience of a significant worsening of symptoms (reflecting a flare in disease activity), response options: no, yes, uncertain. If yes or uncertain, they will be asked which date the flare occurred and the number of days it lasted.	6 months, 12 months, 18 months, 2 years
Adverse events	Number of adverse events, serious adverse events, and withdrawals because of adverse events.	Through study completion, maximum 2 years
Number of consultations/contacts at the hospital	Reported by research nurse or study doctor when in contact with a patient.	From baseline to 2 years
Activity impairment (intervention group)	Item no.6 from Work Productivity and Activity Impairment (WPAI): self-reported activity impairment on a NRS 0-10; higher value indicate worse outcome.	Baseline and monthly until 2 years
Activity impairment (control group)	Item no.6 from Work Productivity and Activity Impairment (WPAI): self-reported activity impairment on a NRS 0-10; higher value indicate worse outcome.	Baseline, 6 months, 12 months, 18 months, 2 years
Costs related to hospital visits	Self-reported travel distance (km and time) and way of transport (walking, bicycle, privat car, public transportation, taxi, airplane, other) in conjunction with consultation at the hospital	Baseline
The need to take time off for hospital visits or video consultation	If in paid work, the need to take time off from work is indicated as yes or no.	Baseline
C-Reactive Protein (CRP) (intervention group)	Blood test at hospital or general practitioner	Baseline, 3, 6, 9, 12, 15, 18, 21 months and 2 years
C-Reactive Protein (CRP) (control group)	Blood test at hospital or general practitioner	Baseline, 6 months, 12 months, 18 months and 2 years
C-Reactive Protein (CRP) (intervention group)	Blood test measured at home in a subgroup among the intervention group	Monthly until 2 years
Modified Health Assessment Questionnaire (MHAQ)	8 question concerning physical function, scored from 0 (no problems) to 3 (impossible to perform)	Baseline, 6 months, 12 months, 18 months, 2 years
PROMIS Physical function	4 questions concerning physical function measured on a 5 point Likert scale	Baseline, 6 months, 12 months, 18 months, 2 years
Pain (intervention group)	Self-reported pain measured on a 11-point NRS (0=no pain; 10=worst possible pain)	Baseline and monthly until 2 years
Pain (control group)	Self-reported pain measured on a 11-point NRS (0=no pain; 10=worst possible pain)	Baseline, 6 months, 12 months, 18 months, 2 years
Joint pain (intervention group)	Self-reported joint pain measured on a 11-point NRS (0=no joint pain; 10=worst possible joint pain)	Baseline and monthly until 2 years
Joint pain (control group)	Self-reported joint pain measured on a 11-point NRS (0=no joint pain; 10=worst possible joint pain)	Baseline, 6 months, 12 months, 18 months, 2 years
Sleep impairment	1 item from Pittsburgh Sleep Quality Index, self-reported sleep impairment in last month due to pain with 4 response categories ranging "Not during the past month" to "Three or more times a week" ; higher value indicate worse outcome.	Baseline, 6 months, 12 months, 18 months, 2 years
Medication use	Medication, contomitant medication and any change in medication during the study period	Baseline, 6 months, 12 months, 18 months, 2 years
Swollen joint count	Physician count of swollen joints; MCP 1-5, PIP 1-5, wrist, elbows, shoulders, ankles, MTP 1-5, at regular visits, extra visits, withdrawls, early discontinuation	Baseline, any hospital visits, 2 years
Tender joint count	Physician count of tender joints; MCP 1-5, PIP 1-5, wrist, elbows, shoulders, ankles, MTP 1-5, at regular visits, extra visits, withdrawls, early discontinuation	Baseline, any hospital visits, 2 years
Extra visits, telephone and video consultations	Number of extra visits to the hospital or video consultations with a healthcare provider	Through study completion, maximum 2 years
Withdrawals/early discontinuation	Number of withdrawals/early discontinuation	Through study completion, maximum 2 years
Physical activity	3 questions assessing frequency, intensity and duration of physical activity last week	Baseline, 6 months, 12 months, 18 months, 2 years
Fatigue	Fatigue last week measured on an 11-point NRS (0=no fatigue, 10=worst possible fatigue)	Baseline, 6 months, 12 months, 18 months, 2 years
Patient acceptable symptom state	one question assessing the patient acceptable symptom state last week, 5 response options from very good to very bad.	Baseline, 6 months, 12 months, 18 months, 2 years
eHealth literacy	eHEALS questionnaire, 9 items measured on a 5 point Likert scale, with higher score indicating better health literacy	Baseline
Patient-reported self-efficacy for using different digital devices, secure login and digital health services	Self-efficacy/confidence in using smartphone, tablet, computer, app's, secure login and digital health services. 6 items with Likert scale response categories: Never used, Very bad, Bad, Neither good nor bad, Good, Very good. Score range 1-5; higher scores indicate higher self-efficacy.	Baseline
Patient satisfaction with care	1 item with five point response options ranging from "Very satisfied" to "Very dissatisfied", higher value indicate better outcome	Baseline, 6 months, 12 months, 18 months, 2 year
Patient satisfaction with remote monitoring	Telehealth usability questionnaire (TUQ) 21 items scored from 1-7, higher score indicate higher satisfaction with telehealth	2 years

Collaborators and Investigators

• Sponsor: Diakonhjemmet Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 29, 2022
• Primary Completion (ANTICIPATED): December 31, 2025
• Study Completion (ANTICIPATED): October 14, 2028

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (ACTUAL): August 11, 2022

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: remote care
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: REK 457358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing of anonymous data may be possible upon reasonable request sent to the principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No