Hypothesis - Our hypothesis is that TNF blocking medication improves cardiac function in patients with active RA. Objectives - Primary objective: to investigate the effect of TNF blocking therapy on diastolic left ventricular (LV) function in RA…
ID
Source
Brief title
Condition
- Heart failures
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is diastolic LV dysfunction, defined as follows:
mild diastolic LV dysfunction (stage I*impaired relaxation). Characterized by
an E/A ratio <1, Em/Am <1, prolonged DT (>240 ms), and IVRT (>110 ms). Em (<8
cm/s) is reduced. E/Em is <10.
Moderate diastolic LV dysfunction (stage II* pseudo normalization).
Characterized by an E/A ratio >1, Em/Am <1. Em (<8 cm/s) is reduced and E/Em is
>10.
Severe diastolic LV dysfunction (stage III* restrictive filling). This stage is
characterized by an overt increased E/A ratio (>2), shortened DT (<150 ms), and
IVRT (<60 ms). Em (<8 cm/s) remains at the lowest level. E/Em is >10.
Secondary outcome
Secondary outcomes:
Systolic LV dysfunction will be defined as an ejection fraction of <50%.
NT-proBNP, IL-6, troponin-I, sTNFR1, sTNFR2 and TNF-α. High NT-proBNP is
defined as 125 pg/ml.
Conduction times will be defined as abnormal if PQ time <0.12 or >0.20 seconds,
QRS duration <0.12 seconds and (corrected) QTc interval <450 milliseconds for
men and 460 milliseconds for women.
Background summary
The mortality rate in patients with rheumatoid arthritis (RA) is increased up
to twofold compared with the general population. This predominately caused by
an increased cardiovascular (CV) risk, with a significantly enhanced rate of
myocardial infarction in comparison to the general population. The systemic
inflammatory state in RA patients is deemed responsible for this increased risk
by accelerating atherosclerosis and causing endothelial dysfunction. Second
after myocardial infarction, congestive heart failure (CHF) is one of the most
prevalent causes of death of RA patients. This could be secondary to myocardial
infarction as this causes damage and subsequent fibrosis (and thus heart
failure) in the heart, or directly by systemic inflammation itself, causing
left ventricular (LV) dysfunction.
Anti-inflammatory treatment with tumor necrosis factor (TNF) blocking therapy
decreases the CV risk. Therefore, TNF blocking therapy potentially decreases
the incidence of CHF by lowering the overall inflammatory state and slowing
down the process of atherosclerosis. On the other hand, TNF is also necessary
for the cardiac homeostasis. Several trials did not show a detrimental effect
of TNF blocking therapy on the incidence of newly onset CHF in RA patients. In
addition, echocardiographic parameters seem to improve during TNF blocking
therapy. In contrast, some cohort investigations suggested an increased
incidence of newly onset CHF in RA patients starting with TNF blocking therapy,
particularly in older RA patients. Altogether, it is presently unknown whether
or not TNF blocking therapy has a favorable effect on CHF in patients with RA.
Our aim is, first, to determine cardiac function in RA patients with high
disease activity at baseline. Second, to investigate the effect of TNF blocking
therapy in regular dosage on cardiac function during six months. Third, as RA
patients on TNF blocking therapy are followed-up for many years, it is possible
to investigate the occurrence of newly onset CHF in RA patients over the
following years.
Study objective
Hypothesis - Our hypothesis is that TNF blocking medication improves cardiac
function in patients with active RA.
Objectives - Primary objective: to investigate the effect of TNF blocking
therapy on diastolic left ventricular (LV) function in RA patients with active
disease.
Secondary objectives - To investigate in RA patients with active disease 1) the
effect of TNF blocking therapy on systolic LV function 2) the effect of TNF
blocking therapy on NT-proBNP levels 3) the effect of TNF blocking therapy on
conduction times and heart rhythm.
Study design
Prospective
Study burden and risks
There are some aspects to this protocol that may cause (some) discomfort to the
subjects. First, the subjects have to remain fasted as indicated at the time of
blood collection. Second, the collection of blood may cause some discomfort.
Possible side effects from blood drawing include faintness, inflammation of the
vein, pain, bruising, or bleeding at the site of puncture. There is also a
slight possibility of infection. Third, during thoracic echography the subject
has to stay in a fixed position. Fourth, when measuring blood pressure, the
inflation of the cuff may cause transient paraesthesia in the hand.
Jan van Breemenstraat 2
Amsterdam 1056Ab
NL
Jan van Breemenstraat 2
Amsterdam 1056Ab
NL
Listed location countries
Age
Inclusion criteria
Diagnosis rheumatoid arthritis
Written informed consent
Active disease (DAS28>=3.2) and/or C-reactive protein >10 mg/l and/or Erythrocyte Sedimentation Rate (ESR) > 15 mm/h
Exclusion criteria
Medical history of cardiac disease (i.e. myocardial infarction, heart failure etc)
Use of TNF blocking therapy 3 months prior to start study
Design
Recruitment
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 | NL49652.048.14 |