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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03254589




Registration number
NCT03254589
Ethics application status
Date submitted
16/08/2017
Date registered
18/08/2017
Date last updated
31/07/2019

Titles & IDs
Public title
Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis
Scientific title
Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis
Secondary ID [1] 0 0
HREC/17/SAC/46
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Stiffness, Aortic 0 0
Endothelial Dysfunction 0 0
Cardiovascular Risk Factor 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Methotrexate
Treatment: Drugs - Sulfasalazine
Treatment: Drugs - Other DMARDs

Experimental: Group 1 - Newly diagnosed RA patients started on subcutaneous MTX - open randomisation vs. sulfasalazine. In this group, use of NSAIDs, steroids, and/or other DMARDs, is allowed, if indicated, for symptom control. The overall management, tests and outpatient rheumatology visits schedule will be similar to other patients with RA, in accordance to standard practice .

Active Comparator: Group 2 - Newly diagnosed RA patients started on sulfasalazine - open randomisation vs. subcutaneous MTX. In this group, use of NSAIDs, steroids, and/or other DMARDs (except MTX), is allowed, if indicated, for symptom control. The overall management, tests and outpatient rheumatology visits schedule will be similar to other patients with RA, in accordance to standard practice.

Experimental: Group 3 - RA patients on long-term treatment (> 1 year) with oral MTX, with or without other DMARDs, NSAIDs and/or steroids, switched to subcutaneous MTX (same dose). In these patients, treatment with other DMARDs, NSAIDs and/or steroids will continue. The overall management, tests and outpatient rheumatology visits schedule will be similar to other patients with RA, in accordance to standard practice.

Active Comparator: Group 4 - RA patients on stable treatment (> 1 year) with other (non-MTX) DMARDs, with or without NSAIDs and/or steroids, and continued on the same treatment. The overall management, tests and outpatient rheumatology visits schedule will be similar to other patients with RA, in accordance to standard practice.


Treatment: Drugs: Methotrexate
See arm descriptions

Treatment: Drugs: Sulfasalazine
See arm description

Treatment: Drugs: Other DMARDs
See arm

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in peripheral systolic blood pressure - Change in peripheral systolic blood pressure
Timepoint [1] 0 0
Change from baseline peripheral systolic blood pressure at 6 months
Secondary outcome [1] 0 0
Change in peripheral and central blood pressure - Change in peripheral and central blood pressure
Timepoint [1] 0 0
Change from baseline peripheral and central blood pressure at 6 months
Secondary outcome [2] 0 0
Change in arterial stiffness - Change in pulse wave velocity
Timepoint [2] 0 0
Change from baseline pulse wave velocity at 6 months
Secondary outcome [3] 0 0
Change in arterial wave reflection - Change in augmentation index
Timepoint [3] 0 0
Change from baseline augmentation index at 6 months
Secondary outcome [4] 0 0
Change in adenosine - Change in adenosine concentrations
Timepoint [4] 0 0
Change from baseline adenosine concentrations at 6 months
Secondary outcome [5] 0 0
Change in arginine metabolites - Change in ADMA concentrations
Timepoint [5] 0 0
Change from baseline ADMA concentrations at 6 months

Eligibility
Key inclusion criteria
- Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria.

- Age =18 years.

- Written informed consent, dated and signed before initiating any study-related
procedure.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Contraindication to MTX or sulfasalazine.

- Patient who cannot be followed during 6 months.

- Active alcohol or substance abuse within the last 12 months.

- Participation in a clinical trial within 3 months prior to the start of the study.

- Body mass index >35 Kg/m2.

- Secondary causes of hypertension.

- Grade 2 (moderate) or 3 (severe) hypertension: clinic blood pressure >160/100 mm Hg.

- Resistant hypertension: clinical blood pressure =140/90 mm Hg despite concurrent use
of three antihypertensive agents of different classes, one of which is a diuretic.

- Clinical systolic blood pressure <100 mm Hg or history of symptomatic orthostatic
hypotension.

- Cardiovascular event, procedure, or hospitalization for unstable angina with the last
6 months.

- Atrial fibrillation.

- Heart failure.

- Treatment with nitrates.

- Estimated glomerular filtration rate (eGFR) <45 mL/min.

- Diagnosis of polycystic kidney disease.

- Glomerulonephritis treated with or likely to be treated with immunosuppressant drugs

- Uncontrolled diabetes with HbA1c >9.0% (>75 mmol/mol).

- Uncontrolled dyslipidaemia with total serum cholesterol >7.5 mmol/L or triglycerides
>5.6 mmol/L.

- Clinical diagnosis of dementia, treatment with medications for dementia or, in the
opinion of the study staff, the participant is cognitively unable to follow the
protocol.

- Other medical, psychiatric, or behavioural factors that in the judgment of the study
staff may interfere with study participation.

- Cancer diagnosed and treated within the past 2 years that, in the judgment of the
study staff, would compromise a participant's ability to comply with the protocol and
complete the study.

- Any organ transplant.

- Pregnancy, currently trying to become pregnant, or of child bearing potential and not
using birth control.

- Significant illness within 2 weeks of study start.

- Patients with an unstable active medical condition that could impair evaluation of
study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Southern Adelaide Local Health Network - Bedford Park
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park

Funding & Sponsors
Primary sponsor type
Other
Name
Flinders University
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of South Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
medac GmbH
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The investigators will study the effects of methotrexate on blood pressure, arterial
stiffness and endothelial function in patients with rheumatoid arthritis.
Trial website
https://clinicaltrials.gov/show/NCT03254589
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Arduino A Mangoni, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
0061882047495
Fax 0 0
Email 0 0
arduino.mangoni@flinders.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03254589