Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000309684
Ethics application status
Approved
Date submitted
28/02/2023
Date registered
21/03/2023
Date last updated
28/03/2024
Date data sharing statement initially provided
21/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Cardiopulmonary outcomes of right heart dysfunction in the critically ill: a prospective observational trial
Scientific title
Assessment of long-term cardiopulmonary function using simultaneous maximal effort cardiopulmonary exercise testing and echocardiography in critically ill patients with acute right heart dysfunction.
Secondary ID [1] 309029 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
right heart dysfunction 329079 0
Condition category
Condition code
Respiratory 326059 326059 0 0
Other respiratory disorders / diseases
Cardiovascular 326256 326256 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The exposure is any illness that leads to the development of right heart dysfunction in patients where the illness severity requires their admission to either an intensive care unit (ICU) or respiratory high dependency unit (HDU). The patients that have this exposure (condition) will be followed up for the duration of their hospital stay and then a further time point observation (where they will undergo further testing) at 3-6 months post hospital discharge.

The in hospital component will be standard investigations and care as determined by the treating clinicians. Patients that have a clinically indicated transthoracic echocardiogram during their inpatient stay, and whose echocardiogram shows right heart dysfunction will be approached for participation. If they consent they will undergo a repeat echocardiogram approximately 72 hours after the first study to assess for persistence or resolution of the dysfunction. Other cares and investigations are as per the treating team.

The follow-up process will involve a single outpatient clinic appointment at 3-6 months following hospital discharge. The duration of this appointment is expected to be 1-2 hours. It will involve taking a history and examining the participant, the participant completing 2 hard copy questionnaires (the Pulmonary Arterial Hypertension - Symptoms and Impact [PAH-SYMPACT] questionnaire and the Dyspnoea-12 questionnaire) and the participant undergoing a simultaneous cardiopulmonary exercise test and echocardiogram. This echocardiogram will be performed by the principal investigator.

The cardiopulmonary exercise test will be a maximum effort, symptom limited exercise test performed on a stationary bike ergometer. This ergometer is a recumbent bike ergometer with the capacity to recline and tilt, allowing for more accurate and precise echocardiographic images to be taken. The echocardiographic component of participant follow-up will occur simultaneously with the cardiopulmonary exercise test, similar to convential exercise stress echocardiography. The active exercise component of this test is expected to last 8-12 minutes.

All participants will undergo the same process/testing, however we will be performing a subgroup analysis comparing those whose right heart dysfunction had resolved on the repeat inpatient study with those right heart dysfunction was still present on the repeat inpatient study.

7 participants were recruited on the initial protocol, which included a standard cardiopulmonary exercise test and subsequent echocardiogram, rather than a combined (simultaneous) cardiopulmonary exercise test and echocardiogram. These participants have not yet had follow-up due to unexpected delays in equipment acquision. These participants, if consenting, will undergo the amended protocol however these patients will have their follow-up at approximately 6-12 months post hospital discharge, rather than 3-6 months post hospital discharge (which is the target time interval for the prospectively recruited patients).
Intervention code [1] 325468 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333990 0
Cardiopulmonary exercise test-exercise stress echo (CPET-ESE): peak oxygen uptake (oxygen uptake is abbreviated as VO2) measured in millilitres/kilogram/minute. This will be measured during the stationary bike exercise test using a conventional cardiopulmonary exercise test (CPET) face mask.
Timepoint [1] 333990 0
Clinic follow-up (3-6 months post discharge)
Primary outcome [2] 333991 0
CPET-SE: anaerobic threshold measured in millilitres/kilogram/minute using graphical CPET data in real time. This is performed with the V slope method: using the plot of heart rate, VO2 and carbon dioxide production (VCO2) (typically box 3 of the Wasserman 9 plot result table), where the inflection point of the VCO2 line represents the onset of the anaerobic threshold. At this point the slope of the VCO2 line will exceed 1 due to CO2 production accelerating beyond O2 consumption.
This CPET data will be collected using a conventional CPET face mask.
Timepoint [2] 333991 0
Clinic follow-up (3-6 months post discharge)
Primary outcome [3] 333992 0
CPET-SE: ventilatory efficiency (minute ventilation/carbon dioxide output, abbreviated as VE/VCO2) (measured as a gradient) using a conventional CPET face mask.
Timepoint [3] 333992 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [1] 418964 0
Primary outcome 4 - CPET-SE: respiratory exchange ratio (abbreviated as VCO2/VO2) (no unit) using a conventional CPET face mask.
Timepoint [1] 418964 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [2] 418965 0
Primary outcome 5 - CPET-SE: peak heart rate (measured in beats/minute) using cardiac rhythm monitoring with electrocardiogram leads to measure heart rate.
Timepoint [2] 418965 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [3] 418966 0
Primary outcome 6 - CPET-SE: heart rate reserve at peak exercise (measured in beats/minute) using cardiac rhythm monitoring with electrocardiogram leads to measure heart rate.
Timepoint [3] 418966 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [4] 418967 0
Primary outcome 7 - CPET-SE: heart rate recovery (measured in beats/minute) cardiac rhythm monitoring with electrocardiogram leads to measure heart rate.
Timepoint [4] 418967 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [5] 418968 0
Primary outcome 8 - CPET-SE: oxygen uptake per work unit (VO2/work rate, measured in millilitres/minute/watt) using a conventional CPET face mask.
Timepoint [5] 418968 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [6] 418969 0
Primary outcome 9 - CPET-SE: oxygen pulse (measured in millilitres/beat) using a conventional CPET face mask to measure oxygen uptake and cardiac rhythm monitoring with electrocardiogram leads to measure heart rate.
Timepoint [6] 418969 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [7] 418970 0
Primary outcome 10 - CPET-SE: end-tidal partial pressure of carbon dioxide (abbreviated as end-tidal PCO2) (measured in millimetres of mercury) using a conventional CPET face mask.
Timepoint [7] 418970 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [8] 418971 0
Primary outcome 11 - CPET-SE: breathing pattern (observational)
Timepoint [8] 418971 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [9] 418972 0
Primary outcome 12 - CPET-SE: respiratory rate (measured in breaths/minute)
Timepoint [9] 418972 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [10] 418973 0
Primary outcome 13 - CPET-SE: ventilatory reserve at peak exercise (measured as a percentage of maximal voluntary ventilation) using a conventional CPET face mask.
Timepoint [10] 418973 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [11] 418974 0
Primary outcome 14 - CPET-SE: tricuspid annular plane systolic excursion (TAPSE) measured using M-mode transthoracic echocardiography (measured in millimetres)
Timepoint [11] 418974 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [12] 418975 0
Primary outcome 15 - CPET-SE: Peak velocity of tricuspid regurgitant jet measured using continuous wave Doppler on transthoracic echocardiography (measured in metres/second)
Timepoint [12] 418975 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [13] 418976 0
Primary outcome 16 - CPET-SE: subjective assessment of right ventricular systolic function (subjective assessment) using transthoracic echocardiography
Timepoint [13] 418976 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [14] 418977 0
Primary outcome 17 - CPET-SE: subjective assessment of left ventricular systolic function (subjective assessment) using transthoracic echocardiography
Timepoint [14] 418977 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [15] 418978 0
Primary outcome 18 - CPET-SE: systolic excursion of the lateral annulus of the left ventricle (using tissue Doppler) (measured in centimetres/second)
Timepoint [15] 418978 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [16] 418979 0
Primary outcome 19 - CPET-SE: systolic excursion of the medial annulus of the left ventricle (using tissue Doppler) (measured in centimetres/second)
Timepoint [16] 418979 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [17] 418980 0
Primary outcome 20 - CPET-SE: assessment of mitral regurgitation (subjective assessment) using transthoracic echocardiography
Timepoint [17] 418980 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [18] 418987 0
Primary outcome 21 - CPET-SE: pulse wave Doppler of mitral valve inflow (measured in centimetres/second)
Timepoint [18] 418987 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [19] 418988 0
Secondary outcome 1: Subjective assessment of breathlessness using the Dyspnoea-12 (D12) patient assessment scale
Timepoint [19] 418988 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [20] 418989 0
Secondary outcome 2: Subjective assessment of breathlessness using the PAH-SYMPACT questionnaire
Timepoint [20] 418989 0
Clinic follow-up (3-6 months post discharge)
Secondary outcome [21] 418990 0
Primary outcome 22 - CPET-SE: Cardiac output during exercise, calculated using transthoracic echocardiography techniques to measure the left ventricular outflow tract (LVOT) diameter (measured in centimetres squared) multiplied by the velocity-time integral (VTI, calculated by pulse wave Doppler) of the left ventricular outflow tract (measured in centimetres/second)
Timepoint [21] 418990 0
Clinic follow-up (3-6 months post discharge)

Eligibility
Key inclusion criteria
All of the following must be present to be considered for participation:
1. Age equal to or greater than 18 years at time of recruitment
2. Ability to provide informed consent OR having a legal guardian who can provide informed consent.
3. Admission to the local hospital intensive care unit or respiratory close observations unit.
4. Evidence of right heart dysfunction on their initial (clinically indicated) transthoracic echocardiogram.
5. Expected total hospital admission to be at least 4 days
6. Expected physical and cognitive ability to complete a stationary bike based CPET at the follow-up appointment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No specific exclusion criteria, noting that a patient must meet all inclusion criteria.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This study is a hypothesis generating study, as such a power calculation and required sample size do not exist. However we are aiming to recruit approximately 100 patients.

Descriptive statistics will be used to describe the entire cohort, with either mean/standard deviation or median/interquartile range to describe variables depending on if the data is parametric or non-parametric.

Assessment of correlation across variables (Spearman and Pearson tests).

An a priori defined comparative analysis will occur between patients whose right heart function remained impaired prior to discharge and those whose right heart function had normalised prior to discharge. For this analysis the inferential statistics used will vary depending on if the data is parameteric (in which case the Student's t-test will be used to compare independent means for interval data) or non-parametric (in which case the Mann-Whitney U test will be used for interval data). If a population in this analysis has less than 30 patients the non-parametric test will be used. To compare nominal data the Chi squared test will be used. Fisher's exact test will be used in place of the Chi squared test if a cell of the 2x2 table has less than 5 observations.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
3/07/2023
Date of last participant enrolment
Anticipated
31/07/2024
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
75
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24134 0
Nepean Hospital - Kingswood
Recruitment postcode(s) [1] 39646 0
2747 - Kingswood

Funding & Sponsors
Funding source category [1] 313237 0
Hospital
Name [1] 313237 0
Nepean Blue Mountains Local Health District
Country [1] 313237 0
Australia
Primary sponsor type
Hospital
Name
Nepean Hospital
Address
Nepean Hospital
Derby St, Kingswood NSW 2747
Country
Australia
Secondary sponsor category [1] 314963 0
None
Name [1] 314963 0
Address [1] 314963 0
Country [1] 314963 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312466 0
Nepean Blue Mountains Local Health District Ethics Committee
Ethics committee address [1] 312466 0
Ethics committee country [1] 312466 0
Australia
Date submitted for ethics approval [1] 312466 0
12/11/2021
Approval date [1] 312466 0
02/02/2022
Ethics approval number [1] 312466 0
2021/ETH12111

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124770 0
Dr Benjamin Gerhardy
Address 124770 0
Nepean Hospital
Derby St, Kingswood NSW 2747
Country 124770 0
Australia
Phone 124770 0
+61 429202373
Fax 124770 0
Email 124770 0
[email protected]
Contact person for public queries
Name 124771 0
Benjamin Gerhardy
Address 124771 0
Nepean Hospital
Derby St, Kingswood NSW 2747
Country 124771 0
Australia
Phone 124771 0
+61 429202373
Fax 124771 0
Email 124771 0
[email protected]
Contact person for scientific queries
Name 124772 0
Benjamin Gerhardy
Address 124772 0
Nepean Hospital
Derby St, Kingswood NSW 2747
Country 124772 0
Australia
Phone 124772 0
+61 429202373
Fax 124772 0
Email 124772 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not approved by ethics committee. Not included in consent form.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.