Targeted Ultrasound in Rheumatoid Arthritis (TURA)

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2013-002777-22-GB
• Date of registration: 07/10/2013
• Prospective Registration: Yes
• Primary sponsor: University of Leeds, Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine
• Public title: Targeted Ultrasound in Rheumatoid Arthritis (TURA)
• Scientific title: Targeted Ultrasound in Rheumatoid Arthritis (TURA) - TURA
• Date of first enrolment: 14/11/2013
• Target sample size: 310
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002777-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Clinical arm blinded to US data, imaging arm guided by US data for therapy modifications; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Denmark, France, Germany, Hungary, Italy, Japan, Spain, United Kingdom

Contacts

• Name: Project Management
• Affiliation: Theorem Clinical Research

• Name: Project Management
• Affiliation: Theorem Clinical Research

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients fulfilling the ACR/EULAR classification criteria 2010 for RA

Patients must be:

2. Within the two years of starting on methotrexate AND

3. Within 5 years of diagnosis AND

4. a) In a stable clinical disease activity state (clinical remission/LDAS /other physician deemed state) for at least 8 successive weeks before screening visit (with no change in DMARD +/- steroid therapy)
b) On methotrexate (as monotherapy or combination +/- = prednisolone 5mg oral daily)
c) On an acceptable (maximal tolerated) methotrexate dose, which, in the clinicans opinion, would justify escalation to adalimumab if a flare in disease activity occurs, as detailed in the protocol.

5. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 264
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 46

Exclusion criteria:
1. Patients not on a stable dose of methotrexate within 8 weeks of screening, intolerance or contraindications (as per clinician judgment)

2. Intramuscular, intra-articular or change in oral corticosteroid within 8 weeks of screening visit.

3. Oral Prednisolone dose > 5 mg within 8 weeks of screening

4. Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.

5. Patients who have previously received any biological therapy for RA.

6. History of severe allergic or anaphylactic reactions to human, humanised or murine monoclonal antibodies

7. 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) 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.).

8. 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).

9. 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).

10. Tuberculosis
a) Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients previously treated for tuberculosis with no recurrence in 3 years are permitted.
b) Patients should be screened for latent TB (as per local guidelines) and, if positive, treated in line with local practice guidelines prior to commencing the study.

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

12. Malignancy
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 18.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Humira
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Primary end point(s): Proportion of patients in whom there is a decrease in PD

Main Objective: To determine whether therapy modifications (including addition of Ultrasound-guided treatment change) can change power Doppler in patients with early Rheumatoid arthritis in a stable clinical disease activity state (clinical remission/LDAS/other physician deemed acceptable state).

Secondary Objective: In patients with early RA in a stable clinical state:
1. To evaluate change in Ultrasound (US) parameters over time
2. To determine whether addition of US-guided therapy modifications leads to:
• Reduced structural damage progression
• Better functional outcomes
3. To assess the impact of US on clinical management
4. To identify the predictive factors for achievement of:
• Sustained imaging/clinical remission
• Lack of structural damage progression
• Improvement in functional outcomes
5. Determine biological therapy (adalimumab) usage in each arm
6. To evaluate steroid need/exposure in each arm
7. To evaluate co-morbidity with the a treat to target and US and treat to target approach
8. To evaluate US-based parameters (those in the standard protocol or additional measures) to address questions related to pathology and response further.

Timepoint(s) of evaluation of this end point: W48 after randomisation

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Change from baseline in:
1. Total PD score: W48
2. GS: W48
3. X-ray scores: W48, W96
4. HAQ-DI scores: W48, W96
5. Bone densitometry scores: W48, W96
6. RA-WIS score (if RA-WIS is available in participating country): W48, W96
7. EQ-5D score: W48, W96
8. Proportion of patients requiring biologic therapy: W48, W96
9. Total steroid exposure: W48, W96
10. Co-morbidity Evaluation

Secondary end point(s): Change from baseline in:
1. Total PD score
2. GS
3. X-ray scores
4. HAQ-DI scores
5. Bone densitometry scores
6. RA-WIS score (if RA-WIS is available in participating country)
7. EQ-5D score
8. Proportion of patients requiring biologic therapy
9. Total steroid exposure
10. Co-morbidity Evaluation

Secondary ID(s)

HG/1096

Source(s) of Monetary Support

AbbVie Ltd, Abbott House

Ethics review

Status: Approved
Approval date: 14/11/2013
Contact:

Results

• Results available: Yes
• Date Posted: 01/07/2020
• Date Completed: 30/07/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-002777-22/results