Trial Outcomes & Findings for PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment (NCT NCT04634162)

NCT ID: NCT04634162

Last Updated: 2023-05-16

Results Overview

The primary end point of the study will be the non-inferiority in P2Y12 reaction units (PRU) measured by VerifyNow after discontinuation of cangrelor vs. placebo

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 22 participants
• Primary outcome timeframe: 2 hours
• Results posted on: 2023-05-16

Participant Flow

22 patients were consented and enrolled in the study: 2 patients were eligible for randomization due to the presence of exclusion criteria. A total of 20 patients were randomized and exposed to at least one dose of study medication.

Participant milestones

Measure	Cangrelor First, Then Placebo icagrelor loading dose followed after 1 hour by cangrelor bolus and infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase. Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase.	Placebo First, Then Cangrelor Ticagrelor loading dose followed after 1 hour by placebo infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase. Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase.
Phase 1 Pre-cossover STARTED	10	10
Phase 1 Pre-cossover COMPLETED	10	10
Phase 1 Pre-cossover NOT COMPLETED	0	0
Phase 2 Post-cossover STARTED	10	10
Phase 2 Post-cossover COMPLETED	10	10
Phase 2 Post-cossover NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment

Baseline characteristics by cohort

Measure	Whole Study Population n=20 Participants Using a computer-based randomization system, patients were randomly assigned in a 1:1 fashion to 1 of the following treatment arms: 1) ticagrelor loading dose (LD) followed after 1 hour by cangrelor bolus and infusion; or 2) ticagrelor LD followed after 1 hour by placebo bolus and infusion. Ticagrelor was administered as a 180-mg LD and cangrelor as a 30-μg/kg bolus followed by 4-μg/kg/min infusion. Cangrelor/placebo infusion was continued for a duration of 2 hours. After completing the first phase of the study, patients underwent a 1- to 4-week washout period and then crossed over to the alternative treatment in the second phase (ie, patients assigned to treatment with cangrelor in the first phase were assigned to placebo in the second phase and vice versa).
Age, Continuous	68.4 years STANDARD_DEVIATION 8 • n=93 Participants
Sex: Female, Male Female	11 Participants n=93 Participants
Sex: Female, Male Male	9 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	10 Participants n=93 Participants
Race (NIH/OMB) White	10 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	20 Participants n=93 Participants
Prior myocardial infatction	7 Participants n=93 Participants

PRIMARY outcome

Timeframe: 2 hours

The primary end point of the study will be the non-inferiority in P2Y12 reaction units (PRU) measured by VerifyNow after discontinuation of cangrelor vs. placebo

Outcome measures

Measure	Cangrelor n=20 Participants Ticagrelor loading dose followed after 1 hour by cangrelor bolus and infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase	Placebo n=20 Participants Ticagrelor loading dose followed after 1 hour by placebo infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
Platelet Reactivity Measured by VerifyNow	16.9 P2Y12 reaction units Interval -11.8 to 45.7	12.6 P2Y12 reaction units Interval -16.1 to 41.4

Adverse Events

Cangrelor

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cangrelor n=20 participants at risk Ticagrelor loading dose followed after 1 hour by cangrelor bolus and infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase	Placebo n=20 participants at risk Ticagrelor loading dose followed after 1 hour by placebo infusion Cangrelor: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase Placebo: Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
Respiratory, thoracic and mediastinal disorders Shortness of breath	45.0% 9/20 • Number of events 9 • 30 days	45.0% 9/20 • Number of events 9 • 30 days

Additional Information

Francesco Franchi, MD

Division of Cardiology University of Florida College of Medicine - Jacksonville

Phone: 1-904-244-2060

Email: francesco.franchi@jax.ufl.edu

Results disclosure agreements

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