Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05376514 |
| Other study ID # |
22SM7440 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 7, 2022 |
| Est. completion date |
May 2024 |
Study information
| Verified date |
August 2022 |
| Source |
Imperial College Healthcare NHS Trust |
| Contact |
Colin D Bicknell, MB MD FRCS |
| Phone |
02033126072 |
| Email |
colin.bicknell[@]imperial.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Background: A sub-study of the AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of
ACE-Inhibition on RisK) trial indicated a statistically significant association between
central blood pressure (BP) variability and abdominal aortic aneurysm (AAA) growth. The role
of anti-hypertensive adherence has not been explored in the context of AAA growth.
Objective: To confirm whether higher central BP variability is associated with higher AAA
growth rates and to examine the effect of medication adherence on AAA growth rates in a
prospective longitudinal cohort study.
Methods: Up to 175 patients will be recruited over ten months from two sites with
standardised quality control of AAA, BP and antihypertensive non-adherence measurement.
Patients (>55 years), with AAAs ≥3cm in diameter (including AAA ≥5.5cm, not proceeding to
surgery) will be recruited and undergo AAA ultrasound (US), BP (peripheral and central) and
antihypertensive non-adherence measurements every four months (+/- one month) for 24 months.
Ambulatory BP variability data will be collected. Data on medication adherence and beliefs
around medications will be collected with validated questionnaires.
Analysis: Primarily, the relationship between central diastolic BP visit-to-visit variability
and AAA growth (estimated by multilevel modelling) based on US measurements and secondarily
the relationship between central diastolic BP variability and time taken to reach the
threshold for AAA repair (5.5 cm) or rupture.
Description:
The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK)
trial was designed to investigate the hypothesis that an ACE-inhibitor (perindopril) would
reduce growth rate of small AAAs in a three-arm randomised placebo-controlled trial. While
this didn't show a significant effect, results from an in-trial sub-study (CAVE study)
demonstrated a significant relationship between central BP variability and aneurysm growth
rates. This requires confirmation, in a dedicated study.
Design:
This is a multicentre prospective longitudinal observational cohort study. Each patient will
have a study visit every 4 months with a minimum of 6 clinical visits where the study team
will collect demographic data; psychological data (short form questionnaires that can be
independently filled in); and physical data. The study team will also access routinely
collected NHS cross-sectional imaging for comparison throughout the study, as quality
control. No additional procedures involving ionising radiation will take place.
Study timeline:
There will be a 10-month recruitment period; all subjects will attend visits for a period of
18-24 months. The data collection will continue for 24 months in total. There will be a
6-month period of data analysis and write up.
Recruitment:
A cohort of up to 175 patients will be recruited from two trusts in London comprising four
hospitals - Imperial College Healthcare NHS Trust (ICH) at St Mary's and Charing Cross
hospitals, and London North West University Healthcare Trust (LNWH) at Northwick Park and
Hillingdon hospitals. All visits and measurements will take place at central sites (St Mary's
and Northwick Park hospitals).
Data Collection:
1. Demographic data - e.g. current prescribed anti-hypertensive medication and other
cardiovascular medications, height and weight, medical history, smoking status
2. Psychological data - three short-form questionnaires that can be independently filled in
by participants. Questionnaires will constitute measures of anxiety and depression
(Hospital Anxiety and Depression Score [HADS]), current medication adherence (modified
Voils Adherence Score), and beliefs around medication and adherence (Beliefs about
Medicines Questionnaire [BMQ]).
3. Physical data - sitting mean peripheral and central systolic and diastolic BP,
visit-to-visit central systolic and diastolic BP variability measured as standard
deviation, coefficient of variation and variation independent of the mean will be
measured using a validated arm cuff-based method. Ambulatory BP parameters will be
measured using a validated monitor. USS AAA measurement will take place at bedside in
supine position with outer-to-outer (OTO) calliper placement.
Primary Endpoint Analysis:
The association between central BP variability measured as standard deviation and AAA growth
will be analysed using regression models where BP variability is the exposure and AAA growth
is the outcome.
Random effects multilevel models where level-1 units are AAA repeated measurements nested
within patients (level-2 units) will be used to estimate AAA growth. To explore non-linearity
in AAA growth appropriate modelling will be used eg. linear splines.
Secondary Endpoints Analyses:
Survival analysis techniques such as Cox proportional hazards models will be used to assess
the relationship between central BP variability and time taken for the AAA to reach the
threshold for intervention (5.5 cm) or rupture.
Associations between haemodynamic parameters and aneurysm growth rate will be investigated.
For each of the other measurements of systolic and diastolic central BP variability
(coefficient of variation (SD ÷ mean) and variation independent of the mean calculated as
SD÷(mean x) where x is determined empirically by curve fitting) and for other BP and
haemodynamic parameters studied, the same multilevel model or generalised linear models will
be used to estimate AAA growth. All analyses will be adjusted for an a-priori list of
confounding variables.
