Atrial Fibrillation, Catheter Ablation
Conditions
Keywords
atrial fibrillation, catheter ablation, protamine sulfate, anticoagulation reversal
Brief summary
The objective of this study is to evaluate the safety, efficacy and efficiency of rapid anticoagulation reversal with protamine sulfate versus routine activated clotting time (ACT) monitoring in patients undergoing catheter based ablation of atrial fibrillation.
Interventions
Protamine sulfate is a highly basic protein that forms stable compounds with acidic heparin to rapidly neutralize the anticoagulation effects.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient's referred for radiofrequency ablation (RFA) or cryoablation for atrial fibrillation or atrial flutter (left atrial). * Age ≥ 18 year * Patients who are mentally and linguistically able to understand the aim of the trial, comply with the trial protocol, verbally acknowledge the risks, benefits, and alternatives in this trial.
Exclusion criteria
* Previous intolerance or allergy to heparin products. * Current or prior administration of protamine products * History of femoral access site complications including hematoma, AV fistula, pseudoaneurysm, aneurysm. * Known lower extremity venous thrombosis. * Coagulopathy or blood dyscrasias. * Active malignancy. * Thrombocytosis (platelet count \>600k/ul) or thrombocytopenia (platelet count \<100k/ul) * Planned use of vascular closure device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Ambulation | 0 to 24 hours | Total length of time from procedural termination to patient ambulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants Who Experienced Vascular Access Site Complications | checked at 30 and 90 days | Secondary endpoints will include the number of patients who experience a 90-day occurrence of vascular access site complications defined as hematoma formation, aneurysm, pseudoaneurysm, arteriovenous fistula formation, access-site related major bleeding (defined as Bleeding Academic Research Consortium (BARC) type 3a or 5), or procedural intervention for access complications (surgical repair, thrombin injection, et cetera) |
Countries
United States
Participant flow
Pre-assignment details
153 patients were enrolled in the trial; however, three patients were removed from the trial before treatment allocation due to physician discretion. These patients never received any treatments and were not included in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Control Patients in the control arm will undergo routine post-procedure management prior to removal of vascular sheaths. This includes routine measurements of ACT beginning 90 min after the cessation of the procedure with a goal ACT of \<200s or return to pre-procedural baseline prior to sheath removal. | 73 |
| Protamine Patients in the active comparator arm will receive protamine sulfate for rapid reversal of heparin prior to sheath removal. They will first receive a small test dose with close hemodynamic monitoring followed by therapeutic dose if no reaction occurs. ACT levels will then be monitored with a goal ACT of \<200s or return to preprocedural baseline prior to removal of vascular sheaths.
Protamine Sulfate: Protamine sulfate is a highly basic protein that forms stable compounds with acidic heparin to rapidly neutralize the anticoagulation effects. | 77 |
| Total | 150 |
Baseline characteristics
| Characteristic | Control | Protamine | Total |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 9 | 63 years STANDARD_DEVIATION 12 | 63 years STANDARD_DEVIATION 11 |
| BMI | 31 kilograms/(meter squared) STANDARD_DEVIATION 7 | 32 kilograms/(meter squared) STANDARD_DEVIATION 6 | 32 kilograms/(meter squared) STANDARD_DEVIATION 6 |
| CHAD2Ds2-VASc Score | 2.2 scores on a scale STANDARD_DEVIATION 1.2 | 2.1 scores on a scale STANDARD_DEVIATION 1.2 | 2.1 scores on a scale STANDARD_DEVIATION 1.2 |
| Creatinine | 1.0 mg/dl STANDARD_DEVIATION 0.8 | 1.0 mg/dl STANDARD_DEVIATION 0.3 | 1.0 mg/dl STANDARD_DEVIATION 0.6 |
| Hemoglobin | 13.7 g/dl STANDARD_DEVIATION 1.6 | 14.4 g/dl STANDARD_DEVIATION 1.2 | 14.1 g/dl STANDARD_DEVIATION 1.4 |
| INR | 1.4 ratio STANDARD_DEVIATION 0.6 | 1.3 ratio STANDARD_DEVIATION 0.5 | 1.4 ratio STANDARD_DEVIATION 0.6 |
| NOAC use | 59 Participants | 63 Participants | 122 Participants |
| Platelets | 194 10^3 platelets/mm^3 STANDARD_DEVIATION 67 | 182 10^3 platelets/mm^3 STANDARD_DEVIATION 72 | 188 10^3 platelets/mm^3 STANDARD_DEVIATION 70 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 25 Participants | 31 Participants | 56 Participants |
| Sex: Female, Male Male | 48 Participants | 46 Participants | 94 Participants |
| Warfarin use | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 73 | 0 / 77 |
| other Total, other adverse events | 4 / 73 | 5 / 77 |
| serious Total, serious adverse events | 1 / 73 | 1 / 77 |
Outcome results
Primary
Time to Ambulation
Total length of time from procedural termination to patient ambulation
Time frame: 0 to 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Time to Ambulation | 480 minutes | Standard Deviation 92 |
| Protamine | Time to Ambulation | 316 minutes | Standard Deviation 80 |
p-value: <0.001t-test, 2 sided
Secondary
Count of Participants Who Experienced Vascular Access Site Complications
Secondary endpoints will include the number of patients who experience a 90-day occurrence of vascular access site complications defined as hematoma formation, aneurysm, pseudoaneurysm, arteriovenous fistula formation, access-site related major bleeding (defined as Bleeding Academic Research Consortium (BARC) type 3a or 5), or procedural intervention for access complications (surgical repair, thrombin injection, et cetera)
Time frame: checked at 30 and 90 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Count of Participants Who Experienced Vascular Access Site Complications | 30 days | 4 Participants |
| Control | Count of Participants Who Experienced Vascular Access Site Complications | 90 days | 4 Participants |
| Protamine | Count of Participants Who Experienced Vascular Access Site Complications | 30 days | 6 Participants |
| Protamine | Count of Participants Who Experienced Vascular Access Site Complications | 90 days | 6 Participants |
Comparison: number of participants who experienced a vascular access site complication at 90 daysp-value: 0.74Fisher Exact