The primary objective is to investigate whether treatment with JAK inhibitors improves cardiac function, reduces myocardial inflammation and favourably alters coronary plaque morphology in patients with rheumatoid arthritis. The secondary objective…
ID
Source
Brief title
Condition
- Myocardial disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the change in left ventricular function in
rheumatoid arthritis patients after 1 year of treatment with a JAK inhibitor.
Left ventricular function will be assessed at baseline and follow-up using
cardiac magnetic resonance measurements of global circumferential, longitudinal
and radial strain.
Secondary outcome
Secondary endpoints are grouped into 2 categories. The first category consists
of comparisons between baseline and follow-up data in rheumatoid arthritis
patients treated with a JAK inhibitor for 1 year. The second category consists
of comparisons between rheumatoid arthritis patients and age-matched healthy
volunteers.
For both categories, secondary endpoints included differences in:
- coronary atherosclerosis as asssed with CCTA
- myocardial inflammation, myocardial perfusion and myocardial fibrosis as
assesed with CMR
In addition, secondary endpoints will also include clinical treatment response
in the patients with rheumatoid arthritis, assessed using the American College
of Rheumatology response rate, DAS-28 score and biomarkers such as C-reactive
protein and erythrocyte sedimentation rate.
Background summary
Cardiovascular disease is the main cause of premature death in patients with
rheumatoid arthritis (RA). RA is associated with congestive heart failure,
myocardial inflammation and rapid progression of high-risk atherosclerotic
coronary plaques. The systemic inflammation plays a central role in the
development of cardiac disease in patients with RA. Janus kinase (JAK)
inhibitors are a novel class of drugs that have the potential to profoundly
reduce inflammation. The effect of JAK inhibitors on cardiac disease is however
unknown. The hypothesis of the JAKARTA trial is that treatment with JAK
inhibitors may favorably affect cardiac function, myocardial inflammation and
coronary atherosclerosis.
Study objective
The primary objective is to investigate whether treatment with JAK inhibitors
improves cardiac function, reduces myocardial inflammation and favourably
alters coronary plaque morphology in patients with rheumatoid arthritis. The
secondary objective is to assess differences in cardiac function, myocardial
inflammation and coronary plaque features between rheumatoid arthritis patients
and a control group of age-matched, healthy volunteers.
Study design
In this prospective, observational cohort study, 50 rheumatoid arthritis
patients with active inflammation and a clinical indication for treatment with
a JAK inhibitor will undergo cardiac magnetic resonance imaging (CMR) and
coronary computed tomography angiography (CCTA) before and 1 year after
treatment with a JAK inhibitor. In addition, CCTA and CMR will be performed in
a group of 50 healthy volunteers. This group will serve as control in order to
demonstrate that patients with rheumatoid arthritis without known cardiac
involvement have reduced cardiac function, more mycoardial inflammation and
more advanced atherosclerosis than age and sex matched matched healthy
volunteers.
Study burden and risks
Since treatment with JAK inhibitors is initiated entirely on clinical grounds,
the burden of participation in this study for the rheumatoid arthritis patients
as well as the healthy volunteers consists solely of the CCTA and CMR imaging.
Peripheral intravenous catheters are placed during imaging and subjects may
experience pain, bruising and bleeding at the puncture site. Secondly, the
vasodilator adenosine will be administered during CMR in order to assess
coronary (microvascular) function. Adenosine is known to cause head-ache,
nausea, flushing, dyspnoea, chest discomfort and bradycardia in approximately
1-10% of subjects. Importantly, these side effects cease within minutes after
stopping adenosine infusion. Thirdly, the iodinated contrast used during CCTA
may be nephrotoxic and contrast induced kidney injury is reported to occur in
0.6-2.3%. Patients with an estimated glomerular filtration rate <30
mL/min/1.73m2 and consequently a higher risk of nephrotoxicity are however
excluded from participation. Fourthly, both the iodinated contrast used during
CCTA and the gadolinium based contrast used during CMR may rarely elicit
allergic reactions. Finally, although CMR is free from ionizing radiation,
participating patients will be exposed to an effective dose of ~4.2 mSv due to
serial CCTA imaging and healthy volunteers will receive a dose of ~2.1 mSv from
the single CCTA scan.
These risks are, however, outweighed by the paramount information that the
JAKARTA trial will provide. JAK inhibitors may prove to be an invaluable drug
for preventing cardiovascular events in patients with RA and the JAKARTA trial
can be considered as a first step towards a future prospective large randomized
trial.
Dr Jan van Breemenstraat 2 Dr jan van Breemenstraat 2
Amsterdam 1056AB
NL
Dr Jan van Breemenstraat 2 Dr jan van Breemenstraat 2
Amsterdam 1056AB
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of rheumatoid arthritis according to the ACR/EULAR 2010 criteria
- Moderate to high disease activity defined as a Disease Activity Score 28
(DAS28) >=3.2
- Clinical indication for treatment with a JAK inhibitor
- No changes to pharmacological therapy in last 4 weeks
- Age 18-70 years
Exclusion criteria
- Symptoms of angina or heart failure
- Left main stenosis >50% on CCTA
- History of hypertension, dyslipidaemia, diabetes mellitus, myocardial
infarction, coronary revascularization, cardiac transplantation, pacemaker or
implantable cardioverter defibrillator implantation, valvular disease, heart
failure, second or third degree heart block, (supra)ventricular tachycardia or
frequent premature atrial or ventricular complexes.
- Contraindications to intravenous adenosine administration (e.g. Chronic
Obstructive Pulmonary Disease stage IV) or asthma, systemic hypotension with
mean arterial blood pressure <70mm Hg, second or third degree AV nodal
conduction disturbances)
- Contraindications to CMR or CCTA (e.g. claustrophobia, ferromagnetic
implants, known allergy to iodinated or gadolinium based contrast agents,
weight or size exceeding the limits of the CMR or CCTA scanner.
- Contraindications to treatment with JAK inhibitors (e.g. history of deep vein
thrombosis or pulmonary embolism, known malignancy, planned major surgery,
active infection)
- Current smoking
- Estimated Glomerular Filtration Rate <30 mL/min/1.73m2
- Pregnancy
- Participation in a trial with an investigational drug or treatment.
- History of noncompliance with medical therapy
- Unwilling or unable to provide written informed consent or comply with the
study protocol
- Life expectancy less than 1 year.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL77572.029.21 |