Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05012722 |
| Other study ID # |
MJ550021 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 30, 2022 |
| Est. completion date |
December 13, 2023 |
Study information
| Verified date |
June 2024 |
| Source |
University Hospitals Coventry and Warwickshire NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This observational study is assessing the effects that arterial stiffness may have on
patients with heart failure (HF) and chronic kidney disease (CKD). Arterial stiffness will be
measured by assessing pulse wave velocity (PWV). Carotid- Femoral PWV is the gold standard in
measuring arterial stiffness non- invasively. Many studies have shown increasing PWV is a
predictor of cardiovascular events, but the significance of increasing PWV as a surrogate
marker for the potential worsening (decompensation) of HF or CKD has not been explored.
This study aims to investigate patients with HF and CKD by assessing PWV while in a
decompensated state and again when in a stable condition after 4 weeks of discharge to
investigate a link between decompensation and rise of arterial stiffness.
The research team aim to recruit 120 patients in this study with 40 patients in each of the 3
groups- heart failure with reduced ejection fraction (HFrEF), heart failure with preserved
ejection fraction (HFpEF) and acute kidney injury (AKI). All AKI patients would have had
known CKD (stages 3a, 3b or 4).
The study participants will be initially recruited in hospital while admitted in an acute
state and tests including bloods, ECG, echocardiography and PWV will be performed. The tests
(excluding echocardiography) will be repeated 4 weeks after discharge. There is no
intervention in this study.
The study seeks to improve the understanding of the role of the vasculature in the
development of acute HF in the two common types- HFrEF and HFpEF. As CKD is a common
comorbidity in heart failure patients we felt that a study of the behaviour of arterial
stiffness in this cohort will add to this understanding. If arterial stiffness is found to be
an important component of the HF syndrome therapeutic interest could be focused at managing
arterial stiffness with novel therapy.
Description:
Research Objective:
The objective of this study is to identify whether or not patients whom are admitted to
hospital with acute decompensated heart failure on a background of stable heart failure or
acute kidney injury on a background of stable chronic kidney disease stage 3a,3b or 4 show
high pulse wave velocity values when compared to being in a stable condition in the
community.
This will help improve the understanding in the pathophysiology of decompensated heart
failure and acute kidney injury in CKD.
Scientific Justification:
The role of arterial stiffness in the pathophysiology (in particular, the development) of
decompensated heart failure is poorly understood. It is suspected that in some types of heart
failure (HFpEF) arterial stiffness may be the driving factor for both acute and chronic types
but evidence on this is still incomplete.
CKD is a common comorbidity in heart failure patients- an increase in arterial stiffness in
this group with AKI is likely to have an impact on the heart failure in those with both CKD
and heart failure.
The study aims to assess whether during the decompensated phases of HF or AKI there is an
acute increase in arterial stiffness measured by PWV. If this is indeed found, this study
will add to the knowledge on the contribution of arterial resistance to the mechanistic
pathophysiology in developing acute HF.
The study is designed to improve the understanding of the contribution of the vasculature to
the HF syndrome as well as the contribution of CKD to this. If this study reveals that some
types of heart (cardiac) failure are more cardiovascular failure, efforts to develop novel
therapies can be then directed at the vascular component too.
It may well reveal also that better risk stratification of heart failure may be possible if
vascular stiffness was included within the assessment for heart failure.
Design and Methodology
This is a prospective non-randomised, observational, cohort study.
Patients with decompensated HF or AKI, admitted to cardiac or renal wards at UHCW will be
introduced to the study by a member of the research or clinical team once they are deemed to
be clinically stable enough to consider this.
Study participants will be screened for eligibility criteria (provided later) and if they
meet the inclusion and exclusion criteria they will be approached by a member of the research
team to discuss the study, and if interested will be provided a participant information
sheet. Written consent will be gained at least 24 hours after the study information is
provided If the patient agrees to enrol in the study.
Once the participants are deemed due for discharge within 48 to 72 hours and are clinically
stable, a member of the research team will measure their pulse wave velocity using the
SphygmoCor CVMS machine (Atcor Medical, Sydney, Australia). Three recordings will be taken
for each value and averaged. During their in-patient stay if an up-to date echocardiogram has
not been performed in the last 6 months this will be undertaken by a qualified member of
staff trained in echocardiography.
Additional tests such as electrocardiograms, baseline blood tests (Full blood count, urea and
electrolytes, NT pro BNP and eGFR) and clinical observations (Height, Weight, BMI, Blood
Pressure, Oxygen saturations, Heart Rate, Respiratory Rate, Temperature) will be undertaken
as part of routine in-patient clinical care- these will be recorded. The time estimated for
pulse wave velocity measurements to be taken is estimated at around 15- 20minutes with the
patient lying flat on their bed.
Once the participant is discharged they will be asked to attend a follow up visit around 4
weeks after discharge. This could be at either Cardiology Research Suite 4th Floor, UHCW or
the City of Coventry Health Centre located at Coventry city-centre. At the follow up visit
repeat tests will include routine bloods including NT pro BNP, repeat pulse wave velocity
assessment and clinical observations such as blood pressure, heart rate, temperature, height
and weight will be recorded. After this follow up visit there will be no further routine
follow up of the participant.
Through the hospital CRRS system (medical records) the research team can track if the patient
is admitted again with either decompensated heart failure or acute kidney injury and record
accurately morbidity or mortality data.
The cohorts of patients will be sub-divided into groups. These groups are decompensated
HFrEF, decompensated HFpEF, acute kidney injury in CKD stage 3a,3b or 4, stable HFrEF, stable
HFpEF and stable CKD stage 3a, 3b or 4. The patients admitted to hospital will act as their
own controls during their follow up visit in a stable condition.
In total the study is looking to recruit 40 participants for each of the 3 groups-
decompensated HFrEF, decompensated HFpEF and acute kidney injury on CKD (stage 3a, 3b or 4).
In total this means 120 participants during the hospitalisation phase who are then followed
up.
During the course of data collection in the study the case report forms will be audited to
ensure that the research protocol is being followed. An excel database will be created with
patient codes for analysis once data collection is complete.
Inclusion and Exclusion Criteria:
Principal Inclusion Criteria
- Male or Female age ≥60
- Known or documented diagnosis of Heart Failure ( Heart Failure with reduced ejection
fraction HFrEF or Heart Failure with preserved ejection fraction HFpEF) on admission or
prior to admission. (HFrEF is defined as Left Ventricular ejection fraction (LVEF) of
<40%, HFpEF is defined as LVEF >50% as in accordance with the classification by the
European Society of Cardiology.)
- Patients on optimal evidence based therapy for heart failure
- Known or documented diagnosis of Chronic Kidney Disease stage 3a, 3b or 4, for minimum
period of ≥6 months
Exclusion Criteria
- Severe Peripheral Vascular Disease
- Patients who have had a myocardial infarction or coronary artery bypass surgery within 6
months
- Severe Anaemia Hb 70g/dl
- Dementia or unable to consent lack mental capacity
- Bedbound/ Immobile patients
- Severe Liver Failure
- Severe Chronic Obstructive Pulmonary Disease
- Patients on LTOT (Long Term Oxygen Therapy)
- Renal transplant
- Previous or Current Renal Replacement Therapy (Peritoneal Dialysis or Haemodialysis)
- Sepsis
Ethical issues
This study presents minimal risk to the participants involved. All procedures will have
informed patient consent. The assessment of arterial stiffness will be performed using a
probe placed on the neck and groin regions which will measure pulse wave velocity (measure of
arterial stiffness) by a non-invasive, painless and completely safe process known as
tonometry.
Other tests include Electrocardiogram (ECG), transthoracic echocardiography (if not done
within 6 months) blood tests all of which pose minimal risk and discomfort (except for minor
discomfort during venepuncture for blood tests).
A meeting with patients (Patient & Public Involvement -PPI-meeting) was conducted in December
2020 and valuable feedback was received. The PPI representatives were happy with the current
protocol of the study and felt that the tests and timing of the tests did not confer any risk
to participants. The lack of intervention would encourage patient participation. PPI feedback
was given in the design of the patient information sheet in May 2021.
During the Covid pandemic patients will be asked to return for a second visit to the either
the hospital (University Hospital Coventry and Warwickshire (UHCW) Cardiology R&D 4th floor
suite) or the Community Heart Failure Clinic on Stoney Staton road, in the Coventry city
centre to avoid potential exposure to Covid. Follow up appointments do pose additional strain
on existing services. This was discussed at the PPI meeting and the recommendations were that
the follow up appointments be kept brief. The research team anticipate that the follow up
appointment will last no more than 1 hour. If follow up appointments are missed the research
team will rearrange an appointment as soon as possible for the participant.
Legal issues There are no legal issues identified in the study. All of the study methods will
be in keeping with good clinical practice NIHR guidance and subjected to standards kept
within the Research and Development Department at UHCW.
Management Issues Data collection could be affected by problems with devices such as
computers at UHCW or problem with the PWV machine manufactured by SphygmoCor CVMS (Atcor
Medical, Sydney, Australia). IT device issues will be rectified by consulting the IT
department. For any problems with the Pulse Wave Velocity device, engineering staff at UHCW
will be consulted for support.
