Clinical trial NCT06865118: Home-Based Clinical Management of Cardiac Complications in Systemic Sclerosis
Official title: The Nor-SSCardioCare Pilot Trial: Home-Based Clinical Management of Cardiac Complications in Systemic Sclerosis Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Systemic Sclerosis (SSc)
Pulmonary Arterial Hypertension (PAH)
Home Monitoring Follow-up
Keywords: Systemic Sclerosis
Pulmonary arterial hypertension
Home monitoring
Remote monitoring
Observational study
PAH progression
Disease progression
Home-based markers
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2025-03-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include adult patients diagnosed with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). Participants will be identified primarily through the Norwegian Systemic Connective Tissue Disease and Vasculitis Registry (NOSVAR) and routine in- and outpatient consultations. Additional recruitment will occur via the national rheumatic association, the OUH clinical studies webpage, and Helsenorge. Participants will attend two study visits at Oslo University Hospital (baseline and week 12). Given the rarity of SSc-PAH, broad recruitment is necessary to obtain feasibility data. The target enrollment is \~20 patients.

Brief summary: The goal of this observational pilot trial is to evaluate the feasibility of home monitoring for patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). The study will assess home-based measures that may help detect disease progression earlier and will also evaluate patient satisfaction, usability, and the impact on health-related quality of life.

The study aims to answer:

* How feasible is home monitoring in SSc-PAH patients in terms of adherence, technical feasibility, and validity of home-based measures?
* How do home-based assessments compare to hospital-based assessments in detecting disease progression?
* How do patients experience digital home monitoring?

Participants will:

* Use a digital platform (Zeen Health) for biweekly self-reporting of symptoms and physiological measurements.
* Perform functional tests at home, including the 1-minute sit-to-stand test (1MSTS).
* Wear the ECG247 Smart Heart Sensor for one week to monitor heart rhythm.
* Collect and submit home blood samples every two weeks.
* Attend two hospital visits (baseline and week 12) for clinical assessments, functional testing, pulmonary function tests, echocardiography, and routine blood sampling for clinical assessments.

This 12-week study will assess the feasibility of home monitoring, as well as the validity and reliability of home-based measures. The findings will help design a future study aimed at integrating home-based assessments into routine clinical care.

Detailed description: Study Overview The Nor-SSCardioCare Pilot Trial is a prospective, observational, single-arm feasibility study evaluating the implementation of home monitoring in patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH).

The primary objective is to assess the feasibility of home monitoring in terms of patient adherence, technical feasibility, and the validity and reliability of home-based measures compared to hospital-based assessments.

Additionally, the study will evaluate patient satisfaction, usability of digital home monitoring, and its impact on health-related quality of life (HRQoL).

This 12-week study will generate feasibility data to inform the design of a larger trial aimed at integrating home monitoring into clinical care for earlier detection of disease progression and cardiac complications.

Background and Rationale SSc-PAH is a life-threatening complication of systemic sclerosis (SSc), with a high mortality rate and limited treatment response if diagnosed late.

Currently, disease progression may go undetected between hospital visits, as patients are typically seen every 3-6 months for assessments including: echocardiography, pulmonary function tests (PFTs), 6-minute walk distance (6MWD) test, right heart catheterization (RHC) when needed.

However, fixed-interval follow-ups do not always capture early signs of disease worsening. Digital home monitoring may improve disease management by allowing more frequent patient assessments (biweekly vs. standard hospital visits), earlier detection of PAH progression based on physiological and symptom data, and increased patient engagement and self-management.

The pilot trial will assess home-based measures that may contribute to earlier detection of disease progression, explore their validity and reliability compared to hospital-based assessments, and evaluate patient satisfaction, usability, and impact on health-related quality of life (HRQoL).

This 12-week study will generate feasibility data to inform the development of a larger trial focused on integrating home monitoring into clinical care.

Objectives and Endpoints

Primary Objective:

To evaluate the feasibility of home monitoring for SSc-PAH patients, including:

* Patient adherence and compliance (frequency and completeness of data entries, ECG monitoring compliance).
* Technical feasibility (rate of technical failures, data loss, and missing entries).
* Validity and reliability of home-based measures compared to hospital-based assessments (comparison of home-based 1MSTS vs. hospital-based 6MWD, and home-based NT-proBNP vs. hospital-based NT-proBNP).

Secondary Objectives:

* Evaluate patient satisfaction, usability, and HRQoL of home monitoring.
* Comparison of home-based vs. hospital-based risk stratification (e.g., mMRC vs. WHO functional class, home-based 1MSTS vs. hospital-based 1MSTS, and NT-proBNP).
* PAH progression and PAH events.
* Heart rhythm monitoring, including arrhythmia detection, heart rate variability (HRV), and its correlation with PAH severity.
* Reproducibility of home-based measures to assess reliability across different settings.

Exploratory analysis

• Explore biomarkers and their correlation with PAH severity

Study Design and Methods

Study Type:

* Prospective, observational, single-arm feasibility study.
* Study duration: 12 weeks.
* Sample size: 20 patients diagnosed with SSc-PAH.
* Study site: Conducted at Oslo University Hospital (OUH), Norway.

Study Procedures and Data Collection

This 12-week study will consist of:

* Two hospital visits at Oslo University Hospital (OUH) (baseline and week 12) for clinical assessments, including functional tests, pulmonary function tests (PFTs), echocardiography, routine blood sampling for clinical assessments, including NT-proBNP measurements, and reporting of patient-reported outcomes using validated HRQoL questionnaires (EmPHasis-10, ScleroID, EQ-5D-5L, HAQ, HADS) and patients satisfaction questionnaires (CSQ-8, Usability, Feasibility, and Impact Questionnaire).
* Biweekly home monitoring, where participants will report symptoms via a digital platform (Zeen Health), perform home-based functional tests (1-minute sit-to-stand test, 1MSTS), collect capillary blood samples for biomarker analyses and NT-proBNP, and undergo ECG monitoring for one week.

Quality Assurance and Data Validation

1. Data Entry and Validation

   * Zeen Health Platform: Secure, approved digital platform used for collecting real-time patient-reported data.
   * Regular monitoring of data completeness, technical issues, and adherence.
   * Manual cross-checks of selected entries against medical records for accuracy.
2. Registry Data Management

   * Secure data storage in Tjeneste for Sensitive Data (TSD) at the University of Oslo.
   * Data review meetings to ensure accuracy and completeness.
   * Consistency checks to verify alignment of registry data with predefined variables.
3. Data Dictionary and Coding Standards

   * Standardized variable definitions for home-based and hospital-based measures.
   * Data coded using predefined categories (e.g., WHO-FC classifications, NT-proBNP cutoffs).
4. Source Data Verification

   * Selected data will be cross-checked against hospital medical records.
   * Agreement between home-based and hospital-based assessments will be analyzed.
5. Sample Size Justification

   * 20-patient sample chosen to assess feasibility before scaling to a larger trial.
   * Not powered for clinical efficacy outcomes.
6. Plan for Missing Data

   * Patient reminders: Participants who miss scheduled data entries may receive gentle reminders via the digital platform to improve adherence.
   * Monitoring of missing data patterns: If systematic issues are identified, additional measures may be implemented.
   * No statistical imputation: Missing data will not be imputed but will be analyzed descriptively.

Statistical Analysis Plan

* Descriptive statistics (means, SDs, proportions) will be used for feasibility outcomes.
* Agreement analysis:

  * Bland-Altman plots for home-based 1MSTS vs. 6MWD.
  * Intraclass correlation coefficients (ICC) for home-based NT-proBNP vs. hospital-based NT-proBNP.
* HRQoL and usability outcomes will be analyzed using paired t-tests/Wilcoxon tests.
* Heart rhythm data (arrhythmia type/frequency, HRV) will be analyzed and correlated with PAH risk profiles.

Ethical Considerations and Oversight

* Approved by the Regional Committees for Medical and Health Research Ethics (REK Sør-Øst, Norway).
* Informed consent required before participation.
* No experimental therapies; all participants will receive standard clinical care.
* Patient confidentiality protected under GDPR compliance.

Future Directions Findings from this study will inform the design of a larger clinical trial evaluating whether home monitoring improves early detection of PAH progression and enhances patient outcomes. If successful, future research will assess its clinical utility in routine care and its potential for broader implementation in SSc-PAH management.

Potential benefits of a future trial:

* Cost-effective, remote disease monitoring.
* Earlier intervention for PAH worsening.
* Improved patient engagement and HRQoL.

Eligibility criteria: Inclusion Criteria:

* Fulfilment of the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) SSc classification criteria
* Fulfilment of the 2022 hemodynamic definition of PAH (mean pulmonary arterial pressure (mPAP) \>20 mmHg, pulmonary artery wedge pressure (PAWP) ≤15 mmHg, and pulmonary vascular resistance (PVR) \>2 WU) in the absence of other causes of pre-capillary PH (no significant ILD and no clinical suspicion of pulmonary or left sided heart disease as the predominant cause of PH), independent of diagnostic period and previous treatment
* Participants must be able to understand and follow trial procedures including completion of questionnaires regarding Patient Reported Outcome measures
* Participants must have access to the internet, and experience in using smartphones or other electronic devices with internet access.
* Capable of giving signed informed consent

Exclusion Criteria:

* Severe end organ disease

  1. Severe heart failure with EF \< 30%
  2. End stage kidney disease with eGFR \< 30 mL/min
  3. End stage lung disease with FVC \< 50% or coexisting severe lung diseases (e.g., COPD (including emphysema), GOLD grade 3-4 with FEV1 \<50%)
  4. In the opinion of the investigator, other clinically significant pulmonary abnormalities
* Active treatment for cancer or non-curable cancer
* Contraindications for functional assessment (6MWD and 1MSTS):

  1. Uncontrolled systemic hypertension (systolic \>220 mmHg or diastolic \>120 mmHg) or hypotension (systolic \<90 mmHg), resting tachycardia (\>130 beats per minute).
  2. Surgery, myocardial infarction/unstable angina, pneumothorax or stroke within the past 8 weeks.
  3. Severe musculoskeletal or neurological limitations preventing safe ambulation or any acute illness which might impair performance or safety in the opinion of the investigator.
* Unable to speak, write and read Norwegian
* Pregnancy or planned pregnancy

Primary outcomes:
measure: Feasibility of Home Monitoring: Patient Adherence and Compliance
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Feasibility of Home Monitoring: Technical Feasibility
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based 1MSTS and Hospital-Based 6MWD for Exercise Capacity Assessment
timeFrame: From enrollment to 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based and Hospital-Based Peripheral Oxygen Saturation (SpO₂) at Rest and Nadir During Exercise
timeFrame: From enrollment to 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based and Hospital-Based Heart Rate Measurements at Rest, Peak Exercise, and Recovery
timeFrame: From enrollment to 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based and Hospital-Based Borg Dyspnea Scale Scores During Exercise
timeFrame: From enrollment to 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based and Hospital-Based Visual Analogue Scale (VAS) Scores for Dizziness and Palpitations
timeFrame: From enrollment to 12 weeks
measure: Feasibility of Home Monitoring: Agreement Between Home-Based and Hospital-Based NT-proBNP Measurements
timeFrame: From enrollment to 12 weeks
Secondary outcomes:
measure: Patient Satisfaction with Home Monitoring
timeFrame: 12 weeks
measure: Patient Usability, Feasibility and Impact of Home Monitoring
timeFrame: 12 weeks
measure: Patient Engagement with Healthcare Providers
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Impact of home monitoring on disease burden (EmPHasis-10 Score)
timeFrame: Baseline and 12 weeks
measure: Impact of home monitoring on functional status (mMRC dyspnea scale)
timeFrame: Baseline and 12 weeks
measure: Impact of home monitoring on symptoms (VAS symptom scales)
timeFrame: From enrollment to 12 weeks
measure: Impact of home monitoring on systemic sclerosis disease burden (ScleroID Score)
timeFrame: Baseline and 12 weeks
measure: Impact of Home Monitoring on Health-Related Quality of Life (EQ-5D-5L Index Score)
timeFrame: Baseline and 12 weeks
measure: Impact of Home Monitoring on Health-Related Quality of Life (EQ VAS Score)
timeFrame: Baseline and 12 weeks
measure: Impact of home monitoring on disability (HAQ Score)
timeFrame: Baseline and 12 weeks
measure: Impact of home monitoring on anxiety and depression (HADS Score)
timeFrame: Baseline and 12 weeks
measure: PAH Progression
timeFrame: From enrollment to the end of the study at 12 weeks
measure: PAH Events
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Changes in hospital-based clinical measures: Change in WHO Functional Class (WHO-FC) from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in hospital-based clinical measures: Change in 6-Minute Walk Distance (6MWD) from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in hospital-based clinical measures: Change in 1-Minute Sit-to-Stand Test (1MSTS) from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in hospital-based clinical measures: Change in Pulmonary Function Tests (PFTs) from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in hospital-based clinical measures: Change in NT-proBNP Levels from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in hospital-based clinical measures: Change in risk stratification score (ESC/ERS Four-Strata Model) from baseline to 12 weeks
timeFrame: Baseline and 12 weeks
measure: Changes in Home-Based Clinical Measures
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Agreement Between Home-Based and Hospital-Based Risk Stratification: Determination of 1MSTS cut-offs for risk stratification based on 6MWD
timeFrame: From enrollment to 12 weeks
measure: Agreement Between Home-Based and Hospital-Based Risk Stratification: Agreement between home-based and hospital-based ESC/ERS four-strata risk stratification
timeFrame: From enrollment to 12 weeks
measure: Reproducibility of Home-Based Measures
timeFrame: From enrollment to the end of the study at 12 weeks
measure: Heart Rhythm Monitoring (ECG 247 Smart Heart Sensor)
timeFrame: One-week monitoring during the 12-week study period
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Anna-Maria Hoffmann-Vold, MD, PhD
role: STUDY_CHAIR
References: