Trial Outcomes & Findings for Use of Protamine for Heparin Reversal After Catheter Ablation of Atrial Fibrillation (NCT NCT03140631)

NCT ID: NCT03140631

Last Updated: 2018-10-23

Results Overview

Total length of time from procedural termination to patient ambulation

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 153 participants
• Primary outcome timeframe: 0 to 24 hours
• Results posted on: 2018-10-23

Participant Flow

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.

Participant milestones

Measure	Control Patients in the control arm will undergo routine post-procedure management prior to removal of vascular sheaths. This includes routine measurements of activated clotting time (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.	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. Activated clotting time (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.
Overall Study STARTED	73	77
Overall Study COMPLETED	73	77
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Control n=73 Participants 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.	Protamine n=77 Participants 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.	Total n=150 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 9 • n=73 Participants	63 years STANDARD_DEVIATION 12 • n=77 Participants	63 years STANDARD_DEVIATION 11 • n=150 Participants
Sex: Female, Male Female	25 Participants n=73 Participants	31 Participants n=77 Participants	56 Participants n=150 Participants
Sex: Female, Male Male	48 Participants n=73 Participants	46 Participants n=77 Participants	94 Participants n=150 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
BMI	31 kilograms/(meter squared) STANDARD_DEVIATION 7 • n=73 Participants	32 kilograms/(meter squared) STANDARD_DEVIATION 6 • n=77 Participants	32 kilograms/(meter squared) STANDARD_DEVIATION 6 • n=150 Participants
CHAD2Ds2-VASc Score	2.2 scores on a scale STANDARD_DEVIATION 1.2 • n=73 Participants	2.1 scores on a scale STANDARD_DEVIATION 1.2 • n=77 Participants	2.1 scores on a scale STANDARD_DEVIATION 1.2 • n=150 Participants
Warfarin use	14 Participants n=73 Participants	14 Participants n=77 Participants	28 Participants n=150 Participants
NOAC use	59 Participants n=73 Participants	63 Participants n=77 Participants	122 Participants n=150 Participants
Hemoglobin	13.7 g/dl STANDARD_DEVIATION 1.6 • n=73 Participants	14.4 g/dl STANDARD_DEVIATION 1.2 • n=77 Participants	14.1 g/dl STANDARD_DEVIATION 1.4 • n=150 Participants
Platelets	194 10^3 platelets/mm^3 STANDARD_DEVIATION 67 • n=73 Participants	182 10^3 platelets/mm^3 STANDARD_DEVIATION 72 • n=77 Participants	188 10^3 platelets/mm^3 STANDARD_DEVIATION 70 • n=150 Participants
INR	1.4 ratio STANDARD_DEVIATION 0.6 • n=73 Participants	1.3 ratio STANDARD_DEVIATION 0.5 • n=77 Participants	1.4 ratio STANDARD_DEVIATION 0.6 • n=150 Participants
Creatinine	1.0 mg/dl STANDARD_DEVIATION 0.8 • n=73 Participants	1.0 mg/dl STANDARD_DEVIATION 0.3 • n=77 Participants	1.0 mg/dl STANDARD_DEVIATION 0.6 • n=150 Participants

PRIMARY outcome

Timeframe: 0 to 24 hours

Total length of time from procedural termination to patient ambulation

Outcome measures

Measure	Control n=73 Participants 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.	Protamine n=77 Participants 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.
Time to Ambulation	480 minutes Standard Deviation 92	316 minutes Standard Deviation 80

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Control n=73 Participants 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.	Protamine n=77 Participants 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.
Count of Participants Who Experienced Vascular Access Site Complications 30 days	4 Participants	6 Participants
Count of Participants Who Experienced Vascular Access Site Complications 90 days	4 Participants	6 Participants

Adverse Events

Control

Serious events: 1 serious events

Other events: 4 other events

Deaths: 1 deaths

Protamine

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Control n=73 participants at risk 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.	Protamine n=77 participants at risk 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.
Nervous system disorders Stroke	1.4% 1/73 • Number of events 1 • 3 months	0.00% 0/77 • 3 months
Vascular disorders Major vascular complication	0.00% 0/73 • 3 months	1.3% 1/77 • Number of events 1 • 3 months

Other adverse events

Measure	Control n=73 participants at risk 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.	Protamine n=77 participants at risk 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.
Vascular disorders Minor vascular complication	5.5% 4/73 • Number of events 4 • 3 months	6.5% 5/77 • Number of events 5 • 3 months

Additional Information

Dr. Hakan Oral

Michigan Medicine

Phone: 734-936-8214

Email: oralh@med.umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place