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Trial registered on ANZCTR


Registration number
ACTRN12623000467639p
Ethics application status
Submitted, not yet approved
Date submitted
26/04/2023
Date registered
5/05/2023
Date last updated
5/05/2023
Date data sharing statement initially provided
5/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Lowering blood pressure in patients on extracorporeal membrane oxygenation (ECMO) life support
Scientific title
Dose response of afterload reduction with sodium nitroprusside on left ventricular filling pressure under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support in adults
Secondary ID [1] 309525 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiogenic shock 329807 0
Condition category
Condition code
Cardiovascular 326708 326708 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of sodium nitroprusside infusion to achieve a reduction in mean arterial pressure of at least 20mmHg, or a minimum mean arterial pressure of 60mmHg (whichever is higher). The medication will be administered as a once only, intravenous infusion. Mean arterial pressure will be monitored using a peripheral arterial cannula or the arterial access sheath.

Initial rate of infusion: 20 micrograms/minute
Uptitration of infusion rate by 20 micrograms/minute every 3 minutes until any of the following occur, at which point the infusion will be stopped:
1) The target reduction in mean arterial pressure (20mmHg) is reached, OR
2) The minimum allowed mean arterial pressure (60mmHg) is reached, OR
3) The patient experiences an adverse drug reaction, OR
4) The maximum allowed infusion rate is achieved (200micrograms/min)
Intervention code [1] 325956 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334572 0
Change in left ventricular filling pressure compared to baseline, assessed via direct measurement of LV pressure using a 6Fr pigtail catheter positioned in the LV.
Timepoint [1] 334572 0
Baseline to completion of nitroprusside infusion.
Secondary outcome [1] 421257 0
Change in left ventricular end-diastolic volume using echocardiography
Timepoint [1] 421257 0
Baseline to completion of nitroprusside infusion.
Secondary outcome [2] 421468 0
Change in aortic velocity-time integral (VTI) using echocardiography
Timepoint [2] 421468 0
Baseline to completion of nitroprusside infusion
Secondary outcome [3] 421469 0
Change in VA-ECMO flow, with reading obtained from the ECMO console
Timepoint [3] 421469 0
Baseline to completion of nitroprusside infusion

Eligibility
Key inclusion criteria
Participants will be eligible for this study if all of the following criteria are met:
• Adult (greater than or equal to 18 years old)
• Currently on VA-ECMO or planned to commence VA-ECMO
• Planned to undergo a procedure in the cardiac catheterisation laboratory (eg diagnostic angiography or percutaneous coronary intervention) whilst on VA-ECMO
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be ineligible for the study if any of the following criteria are met:
• Persons <18 years old
• Patient or next of kin is unable to provide consent
• Patients who have been transferred to the cardiac catheterisation laboratory whilst undergoing extracorporeal cardiopulmonary resuscitation (ECPR)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome variable will be change in left ventricular end-diastolic pressure compared to baseline. Secondary outcome variables will be LVEF, LV end-diastolic volume, aortic valve VTI and ECMO flow, all compared to baseline. Statistical analysis will be performed using the student’s t-test. Multivariable linear regression analysis will be used to determine predictors of change in LVEDP. A p-value of <0.05 will be considered statistically significant. Statistical analysis will be performed using SPSS.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2023
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
11
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24600 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 40198 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 313718 0
Hospital
Name [1] 313718 0
Cardiology Department, Royal Prince Alfred Hospital
Country [1] 313718 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Missenden Rd, Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 315532 0
None
Name [1] 315532 0
Address [1] 315532 0
Country [1] 315532 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 312889 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 312889 0
Missenden Rd, Camperdown, NSW 2050
Ethics committee country [1] 312889 0
Australia
Date submitted for ethics approval [1] 312889 0
26/04/2023
Approval date [1] 312889 0
Ethics approval number [1] 312889 0

Summary
Brief summary
Preliminary in vitro data suggests that afterload reduction is independently associated with a reduction in LV filling pressure, with a reduction in mean arterial pressure of 12.5mmHg associated with a 5mmHg reduction in LV filling pressure (Jiang et al; data presented at ISHLT conference, 2023). The aim of this study is to quantify this relationship in humans. This data will allow better optimisation of blood pressure management in VA-ECMO patients, and appropriate selection of those patients who require more invasive and costly techniques to achieve LV unloading.

The primary objective of this study is to quantify the extent to which reduction in mean arterial pressure affects left ventricular filling pressure during VA-ECMO support. The study is a single-arm trial with haemodynamic and echocardiographic endpoints.

Patients on VA-ECMO who are undergoing a clinically indicated cardiac catheterisation procedure will be administered sodium nitroprusside as a continuous infusion, to achieve a reduction in MAP of 20mmHg but not below 60mmHg. LV end-diastolic pressure will be measured at baseline and at maximal infusion dose. The infusion will then be ceased.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126234 0
Dr Pankaj Jain
Address 126234 0
Cardiology Department, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, NSW 2050
Country 126234 0
Australia
Phone 126234 0
+61 2 9515 7929
Fax 126234 0
Email 126234 0
pankaj.jain@sydney.edu.au
Contact person for public queries
Name 126235 0
Dr Pankaj Jain
Address 126235 0
Cardiology Department, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, NSW 2050
Country 126235 0
Australia
Phone 126235 0
+61 2 9515 7929
Fax 126235 0
Email 126235 0
pankaj.jain@sydney.edu.au
Contact person for scientific queries
Name 126236 0
Dr Pankaj Jain
Address 126236 0
Cardiology Department, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, NSW 2050
Country 126236 0
Australia
Phone 126236 0
+61 2 9515 7929
Fax 126236 0
Email 126236 0
pankaj.jain@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data is only being collected for the purposes of this study. There are no plans for future use of individual patient data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18984Study protocol  pankaj.jain@sydney.edu.au



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.