Coronary Artery Disease
Conditions
Keywords
Percutaneous Coronary Intervention, Blood Platelets, Fentanyl
Brief summary
With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, opiates are the analgesic mainstay for acute coronary syndrome (ACS) patients reporting peri-procedural pain or nitrate-resistant chest pain. However, large observational studies suggest that opiate administration during ACS may result in adverse cardiovascular outcomes. Complimenting this, a number of recent mechanistic studies have demonstrated delayed and attenuated effects of oral dual anti-platelet therapy (DAPT) on platelet inhibition endpoints among subjects receiving intravenous morphine. These studies support the hypothesis that morphine delays the gastrointestinal absorption of DAPT medications. However, no data exist on the impact of intravenous fentanyl, a systemic opioid analgesic routinely administered during percutaneous coronary intervention (PCI) procedures, on the platelet inhibition effects of DAPT. The investigators hypothesize that, similar to morphine, fentanyl administered at the time of PCI will reduce and delay the effect of DAPT on platelet function. As such, the primary aim of this study is to test the impact of intravenous fentanyl on residual platelet reactivity by randomizing patients undergoing PCI to a strategy of peri-procedural benzodiazepine plus non-systemic local analgesia or to the current standard of benzodiazepine plus intravenous fentanyl. Given the critical need for rapid and robust inhibition of platelet function during PCI, this trial has true potential to change clinical practice, particularly if the investigators demonstrate reduced DAPT absorption and elevated residual platelet reactivity among patients receiving fentanyl during PCI.
Interventions
OTHERRemoval of Fentanyl from peri-procedural analgesia
Removal of Fentanyl from peri-procedural analgesia (which is otherwise routinely given for PCI)
DRUGFentanyl
IV peri-procedural analgesia
DRUGLidocaine
Local Anesthetic
DRUGMidazolam
IV sedation
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* undergoing clinically indicated PCI; \>18 years of age; able for PO medications and to provide informed consent
Exclusion criteria
* pregnant; any DAPT(clopidogrel, prasugrel, ticagrelor) within 14 days of enrollment; known coagulation disorders; active treatment with oral anticoagulant or low molecular weight heparin; impaired renal or hepatic function; platelets \< 100 x10 3 /mcl; planned use of Glycoprotein 2b3a for PCI; Prior Trans Arterial Valve Replacement (TAVR) or planned TAVR post PCI; and contraindications to ticagrelor or opiates.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ticagrelor Pharmacokinetics | Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours) | Area under the curve for Ticagrelor Absorption |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single Time-point Platelet Reactivity Using Verify Now | Measured at 2 hours | Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units) |
| Platelet Reactivity Using Light Transmission Aggregometry | Measured at 2 hours | Blood test of Platelet Cell Reactivity using Light Transmission Aggregometry (reported as percent of baseline aggregation in response to adenosine diphosphate stimulation) |
| Patient Self-reported Pain | 2 hours | Patient self report of pain using a visual analog scale (VAS). Scale ranges from 0 to 10 with 0 being No pain and 10 being Most severe pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PCI Without IV Opiate IV midazolam and Local Anesthetic, with removal of IV fentanyl from peri-procedural analgesia (which is otherwise routinely given)
Removal of Fentanyl from peri-procedural analgesia: Removal of Fentanyl from peri-procedural analgesia (which is otherwise routinely given for PCI)
Lidocaine: Local Anesthetic
Midazolam: IV sedation | 105 |
| PCI With IV Opiate IV midazolam and Local Anesthetic and IV fentanyl for peri-procedural analgesia
Fentanyl: IV peri-procedural analgesia
Lidocaine: Local Anesthetic
Midazolam: IV sedation | 107 |
| Total | 212 |
Baseline characteristics
| Characteristic | PCI Without IV Opiate | PCI With IV Opiate | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 9.3 | 63 years STANDARD_DEVIATION 10.2 | 64 years STANDARD_DEVIATION 10 |
| Platelet count | 230 K/cu mm STANDARD_DEVIATION 59 | 223 K/cu mm STANDARD_DEVIATION 71 | 226 K/cu mm STANDARD_DEVIATION 65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 15 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants | 17 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 79 Participants | 75 Participants | 154 Participants |
| Region of Enrollment United States | 105 Participants | 107 Participants | 212 Participants |
| Sex: Female, Male Female | 42 Participants | 25 Participants | 67 Participants |
| Sex: Female, Male Male | 63 Participants | 82 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 107 |
| other Total, other adverse events | 0 / 105 | 0 / 107 |
| serious Total, serious adverse events | 13 / 105 | 7 / 107 |
Outcome results
Primary
Ticagrelor Pharmacokinetics
Area under the curve for Ticagrelor Absorption
Time frame: Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours)
Population: Only the subgroup (n=70) of enrolled participants who required PCI and were loaded with ticagrelor had information on the primary endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI Without IV Opiate | Ticagrelor Pharmacokinetics | 3301 ng*hr/mL | Standard Error 271 |
| PCI With IV Opiate | Ticagrelor Pharmacokinetics | 2107 ng*hr/mL | Standard Error 301 |
Secondary
Patient Self-reported Pain
Patient self report of pain using a visual analog scale (VAS). Scale ranges from 0 to 10 with 0 being No pain and 10 being Most severe pain.
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI Without IV Opiate | Patient Self-reported Pain | 2.3 units on a scale | Standard Deviation 3.1 |
| PCI With IV Opiate | Patient Self-reported Pain | 1.5 units on a scale | Standard Deviation 2.3 |
Secondary
Platelet Reactivity Using Light Transmission Aggregometry
Blood test of Platelet Cell Reactivity using Light Transmission Aggregometry (reported as percent of baseline aggregation in response to adenosine diphosphate stimulation)
Time frame: Measured at 2 hours
Population: Only the subgroup (n=70) of enrolled participants who required PCI and were loaded with ticagrelor had information on the primary endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI Without IV Opiate | Platelet Reactivity Using Light Transmission Aggregometry | 27.5 percentage of baseline aggregation | Standard Deviation 14.4 |
| PCI With IV Opiate | Platelet Reactivity Using Light Transmission Aggregometry | 39.3 percentage of baseline aggregation | Standard Deviation 8.7 |
Secondary
Single Time-point Platelet Reactivity Using Verify Now
Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units)
Time frame: Measured at 2 hours
Population: Only the subgroup (n=70) of enrolled participants who required PCI and were loaded with ticagrelor had information on the primary endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PCI Without IV Opiate | Single Time-point Platelet Reactivity Using Verify Now | 78 PRUs | Standard Deviation 72 |
| PCI With IV Opiate | Single Time-point Platelet Reactivity Using Verify Now | 112 PRUs | Standard Deviation 95 |