Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04176978 |
| Other study ID # |
CREC 2019.063T |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2021 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
September 2023 |
| Source |
Chinese University of Hong Kong |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with an increased risk
of myocardial infarction (MI). Using coronary computer tomography angiogram (CCTA), it is
found that a significantly higher prevalence of high-risk coronary plaque (non-calcified
plaque [NCP]), supporting the notion that more aggressive cardiovascular (CV) evaluation
strategy should be considered in these patients.
Carotid ultrasound screening in this population may be a better alternative than traditional
risk score to identify patients at high CV risk as the latter underestimated CV risk.
Previous study from our group have demonstrated that achieving treatment target (minimal
disease activity [MDA]) can prevent progression of carotid atherosclerosis. Nevertheless, 38%
of this Treat to Target (T2T) cohort still had carotid plaque progression.
Project description
it is hypothesized that combination of a T2T stratgy together with high-intensity
rosuvastatin treatment (Group 1: T2T-statin group) is more effective in preventing
progression of coronary and carotid atherosclerosis than T2T stratgy alone (Group 2: T2T-only
group) in high-risk PsA patients with carotid plaque.
The primary outcome is to ascertain the effect of T2T strategy with high-intensity
rosuvastain (Group 1: T2T-statin group) on the change in CIMT over a period of 12 months
compared with T2T strategy alone (Group 2: T2T-only group)
Description:
Treatment protocol This is a 1-year prospective, hospital-based, open-label, randomized,
controlled trial. The trial comprised two arms. Group 1 will receive T2T strategy together
with rosuvastain 20mg daily (T2T-statin group). Group 2 will receive T2T strategy only
(T2T-only group). The method of concealed random allocation will be used. Simple
randomization will be conducted by a computer-generated random list.
Use of statins The patients will be given the necessary number of rosuvastatin tablets at
each visit. At the following visits, surplus medication will be returned to the investigator.
Compliance is calculated as a percentage, based on the number of tablets returned.
No trials to date that have evaluated effects on CVD events have tested any medication in
combination with statins or treatment to specific LDL-C goals, therefore we do not intensify
the regimen for any particular level of LDL-C response. Measuring LDL-C response after
initiating therapy in this study is mainly to assess adherence. In this primary prevention
trial, in patients who do not tolerate statins, no lipid-lowering therapy will be
administered. Potential interventions include lifestyle modification.
Use of DMARDs All participants will receive a 1-year protocolized treatment with the aim to
achieve MDA. A predefined treatment protocol is developed based on the EULAR recommendations
and the Hong Kong guideline for the use of bDMARDs. Patients fulfilling the criteria for
bDMARDs can either pay out of pocket or can apply for the Samaritan Fund for financial
assistance, provided they must pass a household-based financial assessment
(http://www.ha.org.hk/visitor/ha_visitor_index.asp?content_id=212020). When patient cannot
achieve treatment goal within 3-6 months of therapy, the treatment therapy will be escalated
to the next step according to the protocol, unless the patient declined or toxic effects
preclude this approach. For the introduction of DMARD only joint involvement is taken into
account. The participants with active disease who failed non-steroidal anti-inflammatory drug
(NSAID) or those with poor prognostic factor will start with methotrexate monotherapy, which
is increased to 20mg/week or maximum tolerated dose. Subsequent steps for patients who fail
to achieve treatment goal include switching to other conventional synthetic DMARDs
(csDMARDs), combination csDMARD therapy or TNFi, ustekinumab, secukinumab or tofacitinib.
Intra-articular steroid or local steroid injection to enthesitis and dactylitis are allowed
during the study but will be forbidden in the 4 weeks before assessment.
Clinical Assessment Assessment performed at each visit include pain, physicians' and
patients' global assessments, number of tender joints count (TJC) and swollen joints count
(SJC) (using the 68 tender/66 SJC), Maastricht Ankylosing Spondylitis Enthesitis Score
(MASES), number of digits with dactylitis; ankylosing spondylitis disease activity score
(ASDAS), modified health assessment questionnaire (M-HAQ); Disease Activity index for
Psoriatic Arthritis (DAPSA), Psoriasis Area (BSA), Psoriasis Activity and Severity Index
(PASI) were used to measure joint and skin disease activity.(31) MDA was used for assessment
of treatment efficacy endpoint. The MDA criteria assess 7 domains [TJC ≤ 1, SJC ≤ 1,
enthesitis count ≤ 1, skin (≤ 1 or BSA ≤ 3%), function (measured by the Health Assessment
Questionnaire), ≤ 0.5, patient's global VAS on a 100-mm scale ≤ 20, and patient pain VAS on a
100 mm scale ≤ 15]. If 5 of 7 of the cutoffs for these domains are met, then the patient is
deemed to be in MDA.
Cardiovascular assessments The following anthropomorphic assessment will be performed at each
visit. Anthropomorphic measurements include body heights, body weight, waist and hip
circumferences, two consecutive blood pressure readings in sitting position and heart rate.
Hypertension status is defined as systolic blood pressure (SBP) ≥140mmHg or diastolic blood
pressure (DBP) ≥90mmHg or the use of antihypertensive agents. Other data include menopausal
status, smoking and drinking habits, history of DM, hypertension, hypercholesterolemia, overt
CVD, and family history of CVD, DM in first-degree male relatives <55 years of age or
first-degree female relatives <65 years of age. Drug history is retrieved from case notes or
elicited during the clinical assessment.
Laboratory assessments and inflammatory markers Laboratory assessments at each visit include
complete blood count, liver and renal function tests, creatine kinase (CK), ESR and
C-reactive protein (CRP), fasting blood glucose, lipid profile (total cholesterol [TC],
LDL-C, high-density lipoprotein-cholesterol [HDL-C], triglycerides), fibrinogen and uric
acid.
Carotid intima-media thickness (CIMT) and plaque CIMT and plaque will be assessed at baseline
and 12 months.CIMT will be measured using a high-resolution B-mode ultrasound machine
(Philips EPIQ7) by an experienced sonographer blinded to all clinical information using a
30-MHz linear vascular probe (Philips L12-3 broadband linear array transducer). The CIMT will
be measured offline in the distal common carotid artery, bulb, and proximal internal carotid
artery using dedicated software (Philips Xcelera Cardiology Enterprise Viewer Client 4). The
mean and maximal IMT values of 6 arterial segments will be calculated for further analysis.
Plaque is defined as a localized thickening >1.2 mm that do not uniformly involve the whole
artery. Progression of plaque is defined as an increase in region harboring plaque or number
of plaque. Reproducibility of IMT was 0.97. Total plaque area (TPA) will be measured as
described before. The plane for measurement of each plaque will be chosen by reviewing the
video of the scan to find the largest extent of plaque as seen on the longitudinal view. TPA
will be recorded as the sum of the areas of all plaques in the right and left carotid
arteries. Reading of the ultrasound scans obtained at baseline and follow-up will be
performed concurrently by a single reader (ITC) who is aware of the temporal order of the
images but is blinded to all clinical data. The change in TPA will be calculated by
subtracting the baseline TPA from the follow-up TPA. The intraobserver intraclass correlation
coefficient for TPA was 0.94.
Coronary atherosclerosis assessment CCTA scans will be performed at baseline and 12 months
256-rows multidetector CT (General Electric (GE) Revolution CT) in accordance with the
protocol employed in the ACCURACY trial, and will be analysed by an experienced radiologist
blinded to clinical data (PT). Coronary artery calcium score (CAC) will be quantified by the
Agatston method. The presence, site, stenosis level of plaques will be recorded. Coronary
arteries will be standardised to American Heart Association 15-segment model. Segment
involvement score (SIS) represented the total number of segments harbouring plaque. Lesions
rendering over 50% stenosis of the lumen will be considered as obstructive. For multiple
plaques, the most stenotic one will be recorded. Voxels with attenuation less than 130 HU
will be assigned to the non-calcified volume of the plaque. For each segment, the presence or
absence of 4 coronary artery high risk plaque features will be assessed: positive remodeling,
low attenuation plaque, spotty calcification, and the "napkin ring" sign. Positive remodeling
is defined as an outer vessel diameter that is 10% greater than the mean of the diameter of
the segments immediately proximal and distal to the plaque. Low-attenuation plaque is defined
as a focal central area of plaque with an attenuation density of <30 HU. Spotty calcification
is defined as focal calcification within the coronary artery wall <3 mm in maximum diameter.
The "napkin ring" sign is defined as a central area of low attenuation plaque that had a
peripheral rim of high attenuation. Observer agreement for the assessment of coronary artery
plaque characteristics has overall been shown to be fair. Plaque volume will be measured
automatically based on attenuation (CardIQ Xpress 2.0 Reveal, General Electic).
Toxicity monitoring To monitor the possible side effect of the statin and DMARDs, complete
blood count, CK, liver and renal function tests will be performed every visit. Chest X-rays
will be obtained at baseline and at the end of the study. The treating physician record all
adverse events and serious adverse events and, if necessary, make treatment adjustments in
accordance with the protocol. Serious adverse events are defined as any adverse reaction
resulting in any of the following outcomes: a life-threatening condition or death, a
significant or permanent disability, a malignancy, hospitalization or prolongation of
hospitalization, a congenital abnormality, or a birth defect.
