Clinical trial NCT06533423: Effect of a Self-Management Intervention for Patients Newly Diagnosed With Inflammatory Arthritis: The NISMA Trial
Official title: Effect of a Self-Management Intervention for Patients Newly Diagnosed With Inflammatory Arthritis: Study Protocol for a Randomized Controlled NISMA Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Inflammatory Arthritis
Keywords: self-management
rheumatoid arthritis
axial spondyloarthritis
psoriatic arthritis
newly diagnosed
heiQ
quality of life
Lead sponsor: Glostrup University Hospital, Copenhagen
Sponsor class: OTHER
Collaborators: name: University Hospital Bispebjerg and Frederiksberg
name: Aarhus University Hospital
First posted: 2024-08-01
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization, allocation, and blinding Randomization 1:1 will be performed after baseline assessments and conducted using a computerized random number generator algorithm by the project manager. Randomization will be stratified by site. Therefore, a customized randomization table will be uploaded for each site to REDCap (Research Electronic Data Capture).

The project manager will enroll participants and inform them whether they have been allocated to the intervention group or the control group (see Fig. 2 for participants flow through the trial). For participants randomized to the intervention group, the first individual session will be scheduled as soon as possible after allocation.

Due to the character of the intervention, it is not possible neither to blind participants to their allocated intervention nor to blind the HP delivering the intervention. Analysis of data will be performed blinded to group allocation.
Primary purpose: TREATMENT

Brief summary: Background:

In patients newly diagnosed with inflammatory arthritis, a self-management intervention is anticipated to enhance self-management skills, thereby improving patient function, well-being, and survival. The primary objective of the trial is to investigate the short-term efficacy of the NISMA intervention and usual care, compared to usual care alone (control group), on self-management skills and techniques in patients newly diagnosed with inflammatory arthritis.

Method:

This study aims to test the efficacy of the "Newly diagnosed with Inflammatory arthritis - a Self-MAnagement intervention" (NISMA) through a multicenter pragmatic randomized controlled trial (RCT). The trial will involve 130 patients newly diagnosed with IA from three Danish hospitals. Participants will be randomly assigned to either the NISMA intervention group or a control group receiving usual care. The NISMA intervention includes three mandatory individual sessions with a nurse, supplemented by two optional group sessions over 12 months.

Primary outcomes will be measured using the Health Education Impact Questionnaire (heiQ), focusing on the "skill and technique acquisition" domain. Secondary outcomes include other heiQ domains, quality of life, loneliness, physical function, pain intensity, pain, self-efficacy, anxiety and depression, fatigue, patient global assessment, disease activity, and medication adherence. Data will be collected at baseline, 12 months, and 18 months post-baseline.

Discussion:

This RCT will provide essential insights into the effectiveness of a targeted self-management intervention for patients newly diagnosed with IA. The NISMA intervention, developed following the Medical Research Council Framework for complex interventions, aims to improve self-management skills and overall QoL. By addressing the unique challenges faced by newly diagnosed patients, this study seeks to enhance the initial management of IA, aligning with the European Alliance of Associations for Rheumatology (EULAR) recommendations for self-management support. If successful, the NISMA intervention could represent a significant advancement in the non-pharmacological management of IA, offering a comprehensive, patient-centered approach that addresses both physical and psychological needs.

Detailed description: Background:

Inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), encompasses acute and chronic joint diseases characterized by joint pain, swelling, and tenderness due to inflammation. IA affects over 2% of the global population, with significant variability. It can occur at any age and affects both sexes, with an etiology involving genetic and lifestyle factors. IA primarily causes joint pain and stiffness but can also impact other connective tissues. Without adequate treatment, IA can lead to functional decline, irreversible joint damage, comorbidities, and increased mortality. Early treatment with disease-modifying anti-rheumatic drugs (DMARDs) improves outcomes, with about 60% of RA patients achieving long-term remission. However, symptoms may persist and fluctuate, causing ongoing physiological and psychological distress, impacting daily activities and quality of life (QoL), even in remission.

Newly diagnosed patients with IA face particular challenges, including regular blood tests, lifelong medication, side effects, pain, fatigue, sleep disturbances, and increased risk of comorbidities like depression and cardiovascular disease. They often experience changes in body image, family, work, and social life. A crucial but often lacking aspect of IA care is empowering patients with a thorough understanding of their condition and effective self-management skills. Studies show that newly diagnosed patients benefit from regular consultations and support from health professionals (HPs) to manage the physical, emotional, and social impacts of IA. Enhanced self-management, defined as the ability to manage symptoms, treatments, and lifestyle changes, can improve QoL in chronic illness patients. EULAR recommends incorporating self-management into daily rheumatology care, including patient education and key approaches like problem-solving and action planning. Despite this, no IA-specific self-management interventions focused on newly diagnosed patients exist.

Rationale:

To address this gap, the "Newly diagnosed with Inflammatory arthritis - a Self-MAnagement intervention" (NISMA) was developed. Following the Medical Research Council (MRC) Framework \[29,30\] for developing and evaluating complex interventions, the researchers developed NISMA and tested its feasibility and fidelity. Feedback from patients and HPs led to adjustments in session duration, the number of sessions, flexible scheduling, recruitment strategies, and inclusion criteria for axSpA patients. Group sessions were made optional, and more emphasis was placed on certain behavior change techniques.

The hypothesis is that the adapted NISMA intervention will surpass usual care in enhancing self-management skills. The next step is to test this hypothesis in a randomized controlled trial (RCT). If effective, a cost-effectiveness analysis will be conducted.

Objectives:

The primary objective of this trial is to investigate the short-term efficacy of the NISMA intervention and usual care, compared to usual care alone, on "self-management skills and techniques" in patients newly diagnosed with inflammatory arthritis, from baseline to completion of the intervention (after 12 months).

Our key secondary objectives are to compare the short-term efficacy of the NISMA intervention, relative to usual care on self-management skills, quality of life, loneliness, physical function, pain intensity, pain self-efficacy, anxiety and depression, fatigue, patient global assessment, disease activity, C-reactive protein (CRP), and medication adherence from baseline to completion of the intervention (after 12-months).

Other objectives are to test the longer-term efficacy of the intervention relative to usual care, on self-management skills, quality of life, loneliness, physical function, pain intensity, pain self-efficacy, anxiety and depression, fatigue, patient global assessment, disease activity, C-reactive protein (CRP), and medication adherence at follow-up 18-months after baseline.

Trial design:

The trial is designed as a multicenter pragmatic randomized trial with a two-group parallel design in a superiority framework. Participants will be allocated in a 1:1 ratio; after providing informed consent and completing baseline assessments, they will be randomized to either the NISMA intervention (experimental group) or usual care (control group) with no protocolized treatment.

Setting:

Patients will be included from the following centers: the Center for Rheumatology and Spine Diseases, Rigshospitalet University Hospital, Copenhagen, and department of Rheumatology and Spine Diseases, Holbæk Hospital; both in Denmark.

Sample size and power calculation:

As no established thresholds exist for clinically relevant changes in heiQ domains, we refer to prior research \[61,62\]. In the skills acquisition domain, we found mean differences between groups ranging from 0.22 to 0.38. Therefore, we decided that a minimal important difference probably corresponds to a target difference of 0.30 with a standard deviation (SD) of 0.55 for the heiQ 'skill and technique acquisition' domain (primary endpoint) from baseline to 12 months after baseline. To achieve a statistical power of 80% and a significance level set at an alpha of 0.05, our calculations indicated a need for 54 patients per group (i.e., enrolling 108 patients in the ITT Population). Incorporating an anticipated dropout rate of 15% from our feasibility study, the sample size would correspond to 127. Consequently, we revised the necessary sample size to approximately 65 patients per group (i.e., 130 patients in the ITT population) to achieve a reasonable statistical power to identify a statistically significant difference between the intervention and control group (i.e., corresponding to a statistical power of 87% in the best-case scenario).

Statistical Methods:

Descriptive statistics for baseline data will be reported in a Table 1 format; reported separately for each treatment group. These descriptive statistics will summarize the characteristics of participants at baseline, including demographic information and outcome variables relevant to the trial. Descriptive statistics include the mean and standard deviation (SD), or median and interquartile ranges (if applicable). For categorical data we will report the count and percentages.

The main analyses will be based on the Intention to Treat (ITT) population, i.e., including all randomized patients with a baseline measure available \[63\]. The ITT principle asserts the effect of a treatment policy (that is, the planned treatment regimen), rather than the actual treatment given (i.e., it is independent of treatment adherence) \[9\]. Accordingly, participants allocated to a treatment group (NISMA and Control, respectively) will be followed up, assessed, and analyzed as members of that group, irrespective of their adherence to the planned course of treatment (i.e., independent of withdrawals and cross-over phenomena).

All 95% confidence intervals and P values will be two-sided. We will not apply explicit adjustments for multiplicity, rather we will analyze the key secondary outcomes and interpret these as endpoints in a prioritized order (e.g., "gatekeeping procedure"): The analyses of the secondary endpoints will be performed and interpreted in sequence until one of the analyses fails to show the statistically significant difference, or until all analyses have been completed at a statistical significance level of 0.05 (P\<0.05). All analyses in the statistical hierarchy will be based on the treatment policy estimand (the primary estimand, i.e., the ITT principle), which quantifies the average treatment effect regardless of adherence to treatment or initiation of rescue interventions between baseline and month 12.

The primary endpoint will be based on the change in heiQ from baseline to 12 after baseline, estimated as the difference between least squares means. In our main analyses, estimations of between-group differences for all continuous outcomes will be conducted after 12 months.

Continuous outcome measures will be analyzed using analysis of covariance, with randomized treatment, trial site, and type of IA diagnoses as factors, and baseline (pre-exposure) value as a covariate. Categorical endpoints will be analyzed using logistic regression, with the same factors and covariates. A multiple imputation approach will be used in which missing data are imputed from month 12 measurements from participants in the same treatment group. A series of complete data sets will be generated and analyzed, and the results will be combined using the Rubin formula \[64\] to obtain overall estimates. While binary outcomes will be analyzed and initially reported using Odds Ratios with 95%confidence intervals (95%CIs), all between-group differences 95%CIs for continuous outcomes will be based on the least-square means, adjusted for baseline levels and stratifying factors to minimize random variation \[65\].

Project Group:

The project group includes two patient research partners, professors in rheumatology, nursing, epidemiology, and postdocs in occupational therapy and nursing. They bring expertise in RCTs, qualitative research, and epidemiology.

Patient Involvement:

Three patients were involved in the initial design and development of the NISMA intervention. During feasibility testing, patients were interviewed to include their views. A patient with RA serves as a research partner, ensuring the patient perspective is maintained throughout the project \[54\].

Dissemination and Protocol Amendments:

Results will be disseminated through peer-reviewed journals, academic conferences, news outlets, social media, multimedia materials, and popular science magazines. Authorship will follow ICMJE guidelines. Any significant protocol modifications will be communicated to the Committee on Health Research Ethics for The Capital Region of Denmark, registered on ClinicalTrials.gov, and detailed in the primary RCT report.

Discussion:

This trial addresses the need for targeted interventions for newly diagnosed IA patients. By enhancing self-management skills early, better long-term outcomes are anticipated. The NISMA RCT aims to evaluate the effectiveness of a targeted self-management intervention. Developed through a feasibility study and process evaluation, the intervention is tailored to newly diagnosed patients and may prove more effective than previous interventions.

The trial aligns with EULAR's emphasis on high-quality, systematic, and personalized care in rheumatology. Educating health professionals in group facilitation, problem-solving, goal-setting, and cognitive-behavioral techniques could enhance multidisciplinary collaboration and patient satisfaction. If effective, a cost-effectiveness analysis will follow, focusing on integrating the intervention into clinical practice.

Limitations:

The main limitations are the inability to blind participants, potential spillover effects, variability in usual care, and the individually adjusted intervention content. However, outcome assessors will be blinded, and participants will be instructed not to disclose their group.

Eligibility criteria: Inclusion Criteria:

Patients will be included if they are adults aged 18 years or older with one of the following conditions:

* Rheumatoid Arthritis (RA) with ICD-10 codes: M05.3, M05.9, M05.8, M06.9 diagnosed within the last 6 months
* Psoriatic Arthritis (PsA) with ICD-10 codes: M073.A, M073.B diagnosed within the last 6 months
* Axial Spondyloarthritis (axSpA) with ICD-10 codes: M45.9, M46.1, M46.8, M46.9, diagnosed within the last 12 months, and has initiated biological treatment

Patients with axSpA will have unique inclusion criteria due to NSAIDs being the first-line pharmacological treatment. For those effectively treated with NSAIDs and exercise, treatment is transitioned to their general practitioner. Therefore, only those who have initiated biological treatment will be included.

Exclusion Criteria:

Patients will be excluded if they:

* have insufficient language skills to discuss the topics in the intervention in Danish
* are receiving chemo-therapy treatment for malignancies
* are pregnant
* have severe mental illness.

Primary outcomes:
measure: Primary outcome and endpoint
timeFrame: Baseline-end of intervention (12 months after baseline).
Secondary outcomes:
measure: Self-management skills measured by the Health Education Impact Questionnaire (heiQ)
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Health Related Quality of Life
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Loneliness
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Physical function
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Pain Intensity
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Pain self-efficacy
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Fatigue
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Fatigue
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline.
measure: Patient global
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline
measure: Disease activity
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline
measure: Medication adherence
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline
measure: Anxiety and depression
timeFrame: Baseline-end of intervention (12 months after baseline), and 24 months after baseline
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Rigshospitalet, Center for Rheummatology and Spine Diseases
city: Holbæk
country: Denmark
facility: Holbæk sygehus
Study officials:
affiliation: Rigshospitalet, Glostrup, Center for Rheumatology and Spine Diseases. COPECARE
name: Bente A Esbensen
role: PRINCIPAL_INVESTIGATOR
References: