Clinical Trial Details
— Status: Suspended
Administrative data
| NCT number |
NCT03755570 |
| Other study ID # |
251230 |
| Secondary ID |
|
| Status |
Suspended |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 21, 2019 |
| Est. completion date |
January 14, 2024 |
Study information
| Verified date |
July 2022 |
| Source |
Royal Cornwall Hospitals Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The primary objective of COGNI-CRT is to assess whether Cardiac Resynchronisation Therapy
(CRT) can improve cognitive function in patients with systolic HF (LVEF ≤35%), when compared
to a control group of patients implanted with an Implantable Cardioverter-Defibrillator (ICD)
or a permanent pacemaker (PPM) with systolic HF (LVEF ≤35%).
This clinical investigation is a prospective, single-centre cohort study. Each participant
will be followed for 6 months. The study will collect data over 3 years; 2.5 years for
enrolment and 6 months until the last participant completes the last 6-month follow-up visit.
N.B: COGNI-CRT does NOT affect the patient's care pathway - the patients who will be selected
for participation are those who have already been referred for the device implant. The ONLY
difference to the patient's care pathway caused by COGNI-CRT is the addition of a battery of
cognitive function tests, which involves asking the patient questions and asking them to
complete questionnaire-like cognitive tests.
NTpro-BNP levels, NYHA classification and LVEF will be measured prior to device implantation
and at 6-months post-implant to assess the device's impact on the participant's heart failure
(and CRT response). N.B: NT-proBNP, NYHA classification and LVEF are all parts of the
patient's standard care pathway, COGNI-CRT is just utilising the data collected as part of
the investigation.
The main study arm and control group allows COGNI-CRT to assess 3 potential outcomes for
patients with severe HF (LVEF <35%):
1. Cognitive function is not improved by CRT, ICDs or PPMs
2. Cognitive function can be improved by the assurance of rate control offered by CRT, ICDs
and PPMs
3. Cognitive function can be improved by the assurance of ventricular synchronisation and
rate control provided by the additional left ventricular lead in CRT devices.
Description:
Purpose:
The purpose of this clinical investigation is to assess whether cardiac resynchronisation
therapy (CRT) can improve cognitive function in patients with systolic heart failure (Left
Ventricular Ejection Fraction (LVEF) ≤35%), when compared to a control group of patients
implanted with an implantable cardioverter-defibrillator (ICD) or permanent pacemaker (PPM)
with systolic heart failure (LVEF ≤35%).
Design:
This clinical investigation is a prospective, single-centre cohort study. The study will be
conducted at the Royal Cornwall Hospital Trust (RCHT) in Cornwall, England. Subjects will be
followed for 6 months.
Cognitive performance will be assessed in patients pre- and post-CRT implant (Group A). An
ICD and PPM control group (Group B) will also be assessed using the same battery of cognitive
function tests to ensure any difference in cognitive function which is identified between
pre- and post- CRT implant is due to the CRT therapy, and not due to a placebo effect (which
can be especially powerful with implanted devices) or due to a learning effect (i.e. patients
tested on the second occasion might improve their scores because they have had more
practice).
N.B: COGNI-CRT does NOT affect the patient's care pathway - the patients who will be selected
for participation are those who have already been referred for the device implant. The ONLY
difference to the patient's care pathway caused by COGNI-CRT is the addition of a battery of
cognitive function tests, which involves asking the patient questions and asking them to
complete questionnaire-like cognitive tests.
LVEF, NT-proBNP and New York Heart Association (NYHA) classification data which is collected
prior to device implantation and at 6-months post-implant will be utilised for analysis to
measure response to CRT and to assess difference between the main arm and control group.
Arms in the study will be:
- Group A: Participants implanted with a CRT who are eligible according to the inclusion/
exclusion criteria
- Group B: Participants implanted with an ICD or a PPM who are eligible according to the
inclusion / exclusion criteria
Objectives:
Primary objective: To assess whether CRT can improve cognitive function in patients with
systolic heart failure (LVEF ≤35%), when compared to a control group of patients implanted
with an ICD or PPM with systolic heart failure (LVEF ≤35%).
Secondary Objectives:
- To assess whether CRT can improve cognitive function
- To assess whether ICD and PPM therapy can improve cognitive function
- To assess if the level of improvement in cognitive function correlates to LVEF
improvement / stability and/or NYHA improvement /stability and/or NT-proBNP level
reduction (CRT response).
Subject Population:
The subject population enrolled in this investigation will comprise of male and female
patients aged 20-89 years old. These subjects are patients who are willing to provide
informed consent and meet the specific eligibility criteria. A minimum of 198 participants
will be enrolled in this investigation.
Data for this study will be collected at:
- Enrolment
- Pre-Assessment for CRT, ICD or PPM Implantation
- Cardiac Implantable Electronic Device (CIED) Implant
- Post-Implant 6-Week Device Check (For device optimisation)
- Post-Implant 6-Month Device Follow-Up Visit After completing the Post-Implant 6-Month
Device Follow-Up Visit, the patient will have completed his/her participation in the
study.
Devices Used:
Implanted CRT-P, CRT-D, ICD and PPM devices may include Biotronik, Boston Scientific,
Medtronic and St Jude Medical.
Patient Screening:
Patients who are referred to RCHT for CRT, ICD or PPM implantation with systolic heart
failure (LVEF ≤35%) will be screened prior to Pre-Assessment by the clinical team.
Prospective patients will be afforded sufficient time to consider participation in COGNI-CRT.
Cognitive Tests Used to Evaluate Cognitive Function:
To be Performed Only At Pre-Assessment:
1. Test of Premorbid Functioning (TOPF): TOPF provides the participant with a list of 70
words that have atypical grapheme to phoneme translations. The participant must attempt
to read the list aloud so pronunciation of the words can be assessed. This tests IQ and
memory as the participant must be familiar with the words, rather than being able to
spell out a word they do not know. It takes approximately 10 minutes to complete
To be Performed at Pre-Assessment and at the Post-Implant 6-Month Device Follow-Up
Visit:
2. Hospital Anxiety and Depression Scale (HADS): The test consists of 14 multiple-choice
questions, each attempting to ascertain about the frequency the participant has felt a
certain symptom within the last 7 days. There are 4 answers to choose from which range
from suffering from the symptom "nearly all the time" to "not at all" and are graded 0-3
depending on the participant's answer.
3. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): Consisting
of 12 sections, to evaluate 5 types of cognitive function: immediate memory;
visuospatial/ constructional; attention; language and delayed memory.
4. Frontal Assessment Battery (FAB): The test has 6 neuropsychological tasks which involve
asking the participant questions, for example "In what way are a banana and an orange
alike?", and learning simple actions in response to hand taps or movements.
5. Trail Making Test (TMT) Parts A & B: Both parts of TMT involve circles dotted over a
piece of paper, the circles for Part A are marked with the numbers 1 - 25 and the
patient must draw a line connecting the numbers in ascending order, i.e. "1-2-3-4-5-6…"
etc. Part B involves numbers and letters dotted around the page, from 1-13 and from A-L.
The patient must connect the numbers and letters in ascending order, alternating between
numbers and letters, i.e. "1-A-2-B-3-C…" etc
Response to CRT Measures will be measured prior to device implantation and at the 6-month
follow-up device follow-up clinic:
LVEF: LVEF will be measured prior to device implant to assess the patient's heart function,
and at the Post-Implant 6-Month Device Follow-Up Visit.
NT-proBNP: NT-proBNP levels from the patient's routine blood tests prior to device
implantation and at the Post-Implant 6-Month Device Follow-Up Visit where blood testing is
routine for heart failure patients every 6 months.
NYHA: A NYHA scale assessment will be performed during the screening clinics prior to device
implant, and at the Post-Implant 6-Month Device Follow-Up Visit using the standardised NYHA
questions designed for the purpose of this trial.
N.B: The above 3 tests (LVEF, NT-proBNP and NYHA classification) are performed routinely as
part of the patient standard care pathway for heart failure, and this data will be utilised
for analysis in this trial. The tests are NOT performed for the purpose of COGNI-CRT.
Device Optimisation:
At the post-implant 6-week device follow-up check, all efforts will be made to ensure the
device is optimised as much as is possible, and the patient listed for MDT if problems are
encountered to attempt to resolve problems.
Data Analysis:
Data will be tested for normality. Tests for group differences will be used to compare
cognitive function between patients before and after CRT implant, and in the control group
before and after ICD or PPM implant. Tests for group differences will also be used in
comparison of the LVEF values, BNP results, NYHA classification, QRS duration, percentage
biventricular pacing and BP measurements. Sample size calculations have estimated the
required CRT sample size to power the study to be 99 participants (with a 95% confidence
interval and a 5% margin of error). The expectation is for 99 patients to sign the informed
consent and complete follow-up = 99 CRT participants. The control group will aim to enrol a
similar figure to the main study group, a further 99 ICD and PPM participants. 99 CRT
patients + 99 ICD or PPM patients = 198 patients are expected to be enrolled and complete the
study.
