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Trial registered on ANZCTR


Registration number
ACTRN12621001261808
Ethics application status
Approved
Date submitted
26/03/2021
Date registered
17/09/2021
Date last updated
27/10/2023
Date data sharing statement initially provided
17/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of routine versus selective protamine administration on bleeding in patients undergoing transcatheter aortic valve implantation
Scientific title
Effect of routine versus selective protamine administration on bleeding in patients undergoing transcatheter aortic valve implantation
Secondary ID [1] 303805 0
none
Universal Trial Number (UTN)
Trial acronym
ACE-PROTAVI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
aortic stenosis 321309 0
Condition category
Condition code
Cardiovascular 319105 319105 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational treatment will be one dose of protamine IV in a 0.6-1.0 ratio of 1mg per 100IU of heparin.

Two 10cc syringes, one with protamine (10mg/mL) and one placebo (10mL NaCl 0.9%) will be prepared by either the anaesthetics team or the nursing staff. Dependent on outcome of randomisation, one syringe will be labelled with ‘A’ and contains protamine, and the other will be labelled ‘B’ and contains placebo, or vice versa. This will be documented, and primary operators will be blinded to the true contents of syringe A and B.

Prior to removal of the large sheath, ACT will be assessed. Then syringe A will be injected and sheath-removal/arteriotomy closure per operator’s discretion will be performed. If haemostasis is achieved, time between sheath removal and confirmed arterial haemostasis will be recorded.
If after 10 minutes no haemostasis is achieved, syringe B may be injected per operator’s request.
Intervention code [1] 320115 0
Treatment: Drugs
Comparator / control treatment

Two 10cc syringes, one with protamine (10mg/mL) and one placebo (10mL NaCl 0.9%) will be prepared by either the anaesthetics team or the nursing staff. Dependent on outcome of randomisation, one syringe will be labelled with ‘A’ and contains protamine, and the other will be labelled ‘B’ and contains placebo, or vice versa. This will be documented, and primary operators will be blinded to the true contents of syringe A and B.

Prior to removal of the large sheath, ACT will be assessed. Then syringe A will be injected and sheath-removal/arteriotomy closure per operator’s discretion will be performed. If haemostasis is achieved, time between sheath removal and confirmed arterial haemostasis will be recorded.
If after 10 minutes no haemostasis is achieved, syringe B may be injected per operator’s request.
Control group
Placebo

Outcomes
Primary outcome [1] 326992 0
procedural haemostasis failure and time to haemostasis (TTH). TTH is defined as elapsed time after sheath removal and first observed and confirmed arterial haemostasis.
Timepoint [1] 326992 0
at discharge or after 72h, whichever comes first
Secondary outcome [1] 393387 0
Risk of all-cause death. This will be assessed using patient medical records and study follow-up visits
Timepoint [1] 393387 0
30-days post-procedure
Secondary outcome [2] 393388 0
the need for transfusion for access-site related bleeding. This will be assessed using patient medical records and study follow-up visits
Timepoint [2] 393388 0
30-days post-procedure
Secondary outcome [3] 393389 0
the hematoma size on vascular ultrasound 3-48h after procedure
Timepoint [3] 393389 0
3-48h post-procedure
Secondary outcome [4] 393390 0
The risk of myocardial infarction. This will be assessed using patient medical records and study follow-up visits
Timepoint [4] 393390 0
30-days post-procedure
Secondary outcome [5] 393391 0
the risk of stroke. This will be assessed using patient medical records and study follow-up visits
Timepoint [5] 393391 0
30-days post-procedure
Secondary outcome [6] 393392 0
length of stay post-procedure. This will be assessed using patient medical records and study follow-up visits
Timepoint [6] 393392 0
30-days post-procedure
Secondary outcome [7] 393393 0
the rate of delayed haemostasis failure. This will be assessed at the end of the procedure if additional procedures or interventions are necessary to obtain haemostasis of the arteriotomy site. This will be assessed by physician at the end of the procedure, and using patient medical records/study follow-up visits.
Timepoint [7] 393393 0
direct post-procedure
Secondary outcome [8] 400263 0
The risk of major bleeding complications. This will be assessed using patient medical records and study follow-up visits
Timepoint [8] 400263 0
30-days post-procedure
Secondary outcome [9] 400264 0
The risk of minor bleeding complications. This will be assessed using patient medical records and study follow-up visits
Timepoint [9] 400264 0
30-days post-procedure
Secondary outcome [10] 400265 0
The risk of major vascular complications. This will be assessed using patient medical records and study follow-up visits
Timepoint [10] 400265 0
30-days post-procedure
Secondary outcome [11] 400266 0
The risk of minor vascular complications. This will be assessed using patient medical records and study follow-up visits
Timepoint [11] 400266 0
30-days post-procedure
Secondary outcome [12] 428237 0
Composite rate of all-cause mortality, bleeding complications, major and minor vascular complications according to VARC-3 criteria at discharge
Timepoint [12] 428237 0
at discharge or after 72h, whichever comes first

Eligibility
Key inclusion criteria
Participants eligible for inclusion in this study are:
- aged 18 years or older.
- undergoing elective trans-femoral TAVI with any commercially available transcatheter heart valve.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants not eligible for inclusion in this study are:
- Documented protamine allergy or anaphylaxis
- Recent PCI (< 3 months)
- Planned arterial access via surgical cut-down
- Pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation forms will be generated by computer-generated code, numbered, and sealed in opaque envelopes, that conceals the treatment designation. Stickers with ‘A’ and ‘B’ will also be provided in the envelope.
For patients randomised to protamine syringe A will contain 100mg (10mg/mL) protamine-sulphate. Syringe B will contain 10mL 0.9% NaCl. For patients randomised to placebo, syringe A will contain 10mL 0.9% NaCl, and syringe B will contain 100mg (10mg/mL) protamine-sulphate.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculation for a 25% reduction of baseline 13±10 min of TTH after sheath removal, with >80% power and a 2-sided a of 0.05 leads, and a drop-out of 15% to a minimum of 400 enrolled patients.
The baseline TTH is based on several published studies: a randomised trial comparing proglide and prostar devices after large-bore arteriotomy (mean TTH was 9.8±17 minutes after ProGlide
11
and 13±19 minutes after ProStar)11 and a prospective registry of the Manta device (mean TTH 2.4 minutes)12.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2021
Actual
10/12/2021
Date of last participant enrolment
Anticipated
30/06/2023
Actual
1/06/2023
Date of last data collection
Anticipated
31/08/2023
Actual
1/07/2023
Sample size
Target
400
Accrual to date
Final
410
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 308203 0
Hospital
Name [1] 308203 0
Alfred Hospital
Country [1] 308203 0
Australia
Primary sponsor type
Individual
Name
Antony Walton
Address
Alfred Hospital
55 Commercial Rd
Melbourne 3004 VIC
Country
Australia
Secondary sponsor category [1] 308984 0
None
Name [1] 308984 0
Address [1] 308984 0
Country [1] 308984 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308184 0
Alfred Health - Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 308184 0
55 Commercial Rd
Melbourne 3004 VIC
Ethics committee country [1] 308184 0
Australia
Date submitted for ethics approval [1] 308184 0
15/07/2021
Approval date [1] 308184 0
13/10/2021
Ethics approval number [1] 308184 0

Summary
Brief summary
In patients with diseased aortic valves, catheter-based replacement of the sick valve (TAVI) is a less invasive alternative for surgical valve replacement. TAVI has become the procedure of first choice in patients with increased operative risk. Because the valve is implanted through a catheter from the groin, there is no need for open heart surgery and recovery is much quicker. However, there remains a risk of major or life-threatening bleeding from the access site, especially because patients require blood-thinners (heparin) during the valve implantation. At the end of the procedure, when blood-thinners are no longer required, the effect of heparin can be reversed by protamine injection, but routine use of protamine has not been tested in TAVI patients in a randomised trial. In this study we will evaluate if routine use of protamine reduces the risk of major bleeding and improves outcomes for patients who underwent TAVI. We will compare safety and effectiveness of routine use of protamine in a randomised controlled trial and will compare outcomes after 30 days. The results of this study will help to improve the safety of the TAVI procedure and its outcomes for patient (reduced morbidity and mortality) and society (reduced demand on constrained economic resources).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109842 0
A/Prof Antony Walton
Address 109842 0
Heart Centre, Alfred Hospital
55 Commercial Rd
Melbourne 3004 VIC
Country 109842 0
Australia
Phone 109842 0
+61 3 9076 7361
Fax 109842 0
Email 109842 0
[email protected]
Contact person for public queries
Name 109843 0
Antony Walton
Address 109843 0
Heart Centre, Alfred Hospital
55 Commercial Rd
Melbourne 3004 VIC
Country 109843 0
Australia
Phone 109843 0
+61 3 9076 7361
Fax 109843 0
Email 109843 0
[email protected]
Contact person for scientific queries
Name 109844 0
Antony Walton
Address 109844 0
Heart Centre, Alfred Hospital
55 Commercial Rd
Melbourne 3004 VIC
Country 109844 0
Australia
Phone 109844 0
+61 3 9076 7361
Fax 109844 0
Email 109844 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


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11186Study protocol    381696-(Uploaded-26-03-2021-15-52-53)-Study-related document.pdf



Results publications and other study-related documents

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