Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis

NCT03254589 | Completed Phase 4

• 1 other identifier: HREC/17/SAC/46
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will study the effects of methotrexate on blood pressure, arterial stiffness and endothelial function in patients with rheumatoid arthritis.

Conditions

Rheumatoid Arthritis; Stiffness, Aortic; Endothelial Dysfunction; Cardiovascular Risk Factor

Keywords

Methotrexate; Rheumatoid arthritis; Blood pressure; Arterial stiffness; Cardiovascular risk

Outcome Measures

Primary Outcomes (1)

• Change in peripheral systolic blood pressure

  Change in peripheral systolic blood pressure

  Change from baseline peripheral systolic blood pressure at 6 months

Secondary Outcomes (5)

• Change in peripheral and central blood pressure

  Change from baseline peripheral and central blood pressure at 6 months

• Change in arterial stiffness

  Change from baseline pulse wave velocity at 6 months

• Change in arterial wave reflection

  Change from baseline augmentation index at 6 months

• Change in adenosine

  Change from baseline adenosine concentrations at 6 months

• Change in arginine metabolites

  Change from baseline ADMA concentrations at 6 months

Study Arms (4)

Group 1

EXPERIMENTAL

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 .

Drug: Methotrexate

Group 2

ACTIVE COMPARATOR

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.

Drug: Sulfasalazine

Group 3

EXPERIMENTAL

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.

Drug: Methotrexate

Group 4

ACTIVE COMPARATOR

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.

Drug: Other DMARDs

Interventions

Methotrexate DRUG

See arm descriptions

Group 1; Group 3

Sulfasalazine DRUG

See arm description

Group 2

Other DMARDs DRUG

See arm

Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Flinders University: lead
• University of South Australia: collaborator
• medac GmbH: collaborator

Study Sites (1)

Southern Adelaide Local Health Network

Bedford Park, South Australia, 5042, Australia

Location

Related Publications (2)

• Mangoni AA, Wiese MD, Woodman RJ, Sotgia S, Zinellu A, Carru C, Hulin JA, Shanahan EM, Tommasi S. A controlled comparative study of the effects of methotrexate and pharmacogenetic factors on arterial blood pressure and arterial stiffness in patients with rheumatoid arthritis. Ann Med. 2025 Dec;57(1):2539311. doi: 10.1080/07853890.2025.2539311. Epub 2025 Jul 31.

  PMID: 40742006 DERIVED

• Mangoni AA, Wiese MD, Woodman RJ, Sotgia S, Zinellu A, Carru C, Hulin JA, Shanahan EM, Tommasi S. Methotrexate, blood pressure and arterial function in rheumatoid arthritis: study protocol. Future Cardiol. 2024;20(13):671-683. doi: 10.1080/14796678.2024.2411167. Epub 2024 Oct 10.

  PMID: 39387403 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Sulfasalazine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Pharmacology

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 18, 2017
• Study Start: October 1, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

AU (1)