Targeted Ultrasound in Rheumatoid Arthritis (TURA)

The purpose of this study is to determine whether therapy modifications (including addition of ultrasound-guided treatment change) can change imaging results in patients with early rheumatoid arthritis in a stable clinical disease activity state.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Targeted Ultrasound
• Intervention / Treatment: Drug: Adalimumab

Detailed Description

Rheumatoid arthritis is the most common form of inflammatory arthritis. It is a condition where the body's joints become swollen and damaged. Currently, the approach used to manage rheumatoid arthritis is the so-called 'Treat to Target' approach. The aim of this approach to treatment is to achieve the absence of signs and symptoms, or best possible state of low disease activity. It requires the use of frequent routine clinical assessments to help determine what treatment to use. Ultrasound imaging (using sound waves to take images of the joints and surrounding tissues) has been shown to be better than standard clinical measurements in detecting disease activity. Doctors are already using ultrasound imaging as part of their decisionmaking, in terms of diagnosis and altering treatments, but it is has not been clearly shown if this is associated with a better control of the disease.

Participants will be randomly put into 1 of 2 treatment groups (standard treatment group or the imaging group). All patients will also undergo the ultrasound assessment. In the standard treatment arm, the doctor will not know the ultrasound result and will base treatment on the routine disease activity score alone. In the imaging group, doctors will use routine clinical disease activity score plus the ultrasound result to make decisions on which treatment is given and treatment will be increased if necessary. However, for patients in the imaging group, even if their rheumatoid arthritis remains stable as judged by the disease activity score, treatment will be increased based on signs of active disease on the ultrasound.

Participation will last for 2 years. During the study participants will be required to attend 8 clinic visits. Approximately 400 patients from a number of countries in Europe and Japan are expected to take part in the study.

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals NHS Trust

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:

• Age ≥ 18 years old
• Confirmed Participation by Informed Consent
• Patients fulfilling the ACR/EULAR classification criteria 2010 for rheumatoid arthritis (RA)

Patients must be:

• Within the first year of starting on methotrexate AND
• Within 5 years of diagnosis AND
• In a stable clinical disease activity state (clinical remission/LDAS /other physician deemed state) on methotrexate (as monotherapy or combination +/≤ prednisolone 5mg oral daily) for at least 8 successive weeks (with no change in Disease-Modifying Anti-Rheumatic Drugs (DMARD) +/steroid therapy - see exclusion criteria)
• Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral/parenteral /implantable hormonal contraceptives, intrauterine device or barrier and spermicide). Subjects must agree to use adequate contraception during the study and for at least 5 months after study completion (or longer if on relevant therapy and in line with local regulations).
• Male subjects must agree to ensure they or their female partner(s) use adequate contraception during the study and for at least 5 months after the end of the study period.

Exclusion Criteria

• Patients not on a stable dose of methotrexate within 8 weeks of screening, intolerance or contraindications (as per clinician judgment)
• Intramuscular, intraarticular or change in oral corticosteroid within 8 weeks of screening visit.
• Oral Prednisolone dose > 5 mg within 8 weeks of screening
• Treatment with any investigational agent within 4 weeks (or 5 halflives of the investigational drug, whichever is longer) of screening.
• Patients who have previously received any biological therapy for RA.
• History of severe allergic or anaphylactic reactions to human, humanised or murine monoclonal antibodies
• Evidence of serious +/uncontrolled concomitant disease which in the investigator's judgment would deem the patient inappropriate for inclusion in the study: including (but not exclusively)including cardiovascular (NYHA class III/IV heart failure), nervous system (demyelination), pulmonary (including obstructive pulmonary disease, pulmonary fibrosis), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.).
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
• Any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening. Patients with persistent infections and patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ).
• Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB (as per local guidelines) and, if positive, treated following local practice guidelines prior to commencing the study. Patients previously treated for tuberculosis with no recurrence in 3 years are permitted.

• Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.

  12. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including haematological malignancies and solid tumours, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years unless related to primary disease under investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adalimumab, masked ultrasound; Adalimumab and blinded ultrasound.	Drug: Adalimumab; Other Names: Humira
Experimental: Adalimumab, unmasked ultrasound; Adalimumab and open ultrasound.	Drug: Adalimumab; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients in whom there is a decrease in Power Doppler (PD) at week 48 after randomisation.	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Total PD score at week 48	Week 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
GS (Grey Scale ultrasound)) at week 48		Week 48
X-ray scores at 48 and 96 weeks.		Weeks 48 and 96
HAQ-DI scores at 48 and 96 weeks	Disability Index questionnaire	Weeks 48 and 96
Bone densitometry scores at weeks 48 and 96		Weeks 48 and 96
RA-WIS score at weeks 48 and 96	Rheumatoid Arthritis Work Instability Scale	Weeks 48 and 96
EQ-5D score at weeks 48 and 96	Quality of life questionnaire	Weeks 48 and 96
Proportion of patients requiring biological therapy at 48 and 96 weeks		Weeks 48 and 96
Development of Co-Morbidity Evaluation.	Data collected will include total steroid exposure, number of infection events, blood pressure control.	Week 96

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: AbbVie; Theorem

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: February 4, 2014
• First Posted (Estimate): February 5, 2014

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: HG/1096; RR13/10787 (Other Identifier: Sponsor reference); 2013-002777-22 (EudraCT Number)