Rheumatoid Arthritis-Associated Interstitial Lung Disease: Characterization of Lung Disease Progression (BERTHA)

BERTHA Study: Rheumatoid Arthritis-Associated Interstitial Lung Disease: Characterization of Lung Disease Progression. A Multicenter, Observational Study

BERTHA study´s primary objective is to characterize Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD) progression and to define a combination of biomarkers, genetic and clinical variables capable of identifying patients at risk of RA-ILD progression

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis; Pulmonary Fibrosis; Interstitial Lung Disease; Rheumatoid Lung

Detailed Description

BERTHA is a multicentric, observational study that will enroll 100 RA-ILD patients to be followed for 2 years.

Interstitial Lung Disease (ILD) progression will be ascertained by quantitative image analysis and functional parameters. Variables associated with progression with be identified.

Additionally, RA-ILD endotypes will be investigated as well as their association with RA-ILD progression.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil
    • Universidade Estadual de Campinas (UNICAMP)
  • Florianopolis, Brazil
    • LABOX - Federal University of Santa Catarina (UFSC)
  • Florianopolis, Brazil
    • LAPOGE - Federal University of Santa Catarina (UFSC)
  • DF
    • Brasília, DF, Brazil, 70840-901
      • Hospital Universitário de Brasilia (HUB)
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Hospital das Clinicas - FMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

RA-ILD patients defined by altered imaging and associated functional derangements and/ or symptoms

Description

Inclusion Criteria:

1. Consecutive adult patients (aged >18 years) meeting RA diagnostic criteria in accordance with ACR 2010
2. Presence of interstitial lung disease 2.1 ILD Definition: presence of interstitial alterations in HRCT associated to functional derangements and/or symptoms
3. Patient agrees with having follow-up visits every 6 months for 2 years

Exclusion Criteria:

1. Pregnancy or intending to become pregnant
2. Overlap with other diseases that occurs with ILD (other collagenoses, vasculitis, inflammatory bowel disease)

3. Presence of advanced ILD, characterized by:

   a. Dyspnea rated as modified Medical Research Council 4 (mMRC4) on routine visit

4. Presence of significant Arterial Pulmonary Hypertension:

   1. Evidence of Right ventricular failure evidence by echocardiography
   2. Previous right chamber catheterism showing cardiac index < 2 liters/min/m²
5. Significant co-morbidity impacting respiratory system (e.g., congestive heart failure, lung neoplasm, active tuberculosis)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
RA-ILD; Consecutive adult patients (aged >18 years) with RA* and interstitial lung disease *in accordance with the American College of Rheumatology (ACR) classification criteria of 2010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interstitial Lung Disease progression - FVC	FVC longitudinal behavior (continuous variable)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interstitial Lung Disease progression - imaging	quantitative overall disease progression (continuous variable) & %VRS (vessel related structures) > 4.4% if access to CALIPER software	2 years
Interstitial Lung Disease progression - death	Time to death or lung transplant	2 years
Interstitial Lung Disease progression - FVC dichotomous variable	Proportion of patients with a change from baseline in the %Forced Vital Capacity (FVC): greater or equal to 10% or; between 5 and 10% and worsening of symptoms	2 years

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Collaborators: Bristol-Myers Squibb; Boehringer Ingelheim
• Investigators: Study Chair: Prof. Alexandra Latini, PhD, Federal University of Santa Catarina; Study Chair: Leticia Kawano-Dourado, MD, HCOR Research Institute, Hospital do Coracao, São Paulo, Brazil

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 28, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Fibrosis; Disease Progression; Arthritis; Arthritis, Rheumatoid; Lung Diseases; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: BERTHA_IM101-839

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Under development
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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