Acute Coronary Syndrome, Adverse Reaction to Antiplatelet Agent
Conditions
Keywords
Ticagrelor, antiplatelet, Acute Coronary Syndrome
Brief summary
The aim of the Mashed Or Just Integral pill of TicagrelOr (MOJITO) study is to evaluate the superiority of Ticagrelor 180 mg LD mashed pill versus Ticagrelor 180 mg LD integral pill both orally administrated in decreasing residual platelet reactivity 1 hour after the administration among 70 patients with STEMI (ST segment elevation myocardial infarction) undergoing PPCI (primary percutaneous coronary intervention) with bivalirudin monotherapy.
Interventions
DRUGTicagrelor mashed pills
The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In all case before the end of the PCI (percutaneous coronary intervention) . In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (90 mg Ticagrelor). Mashed pills administration will be prepared placing 2 ticagrelor pills in a mortar and mashing for 60 seconds using a pestle. The total contents of the mortar will be transferred to the dosing cup, 50 mL of purify water will be added, and the suspension mixed up before drinking. Afterwards, 100 mL of purify water will be administered to the patient.
DRUGTicagrelor integral pills
The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In all case before the end of the PCI (percutaneous coronary intervention) . In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (90 mg Ticagrelor).
Sponsors
AstraZeneca
A.R. CARD Onlus Foundation
David Antoniucci
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
* Patients presenting within 12 hours from the onset of symptoms with STEMI * Informed, written consent
Exclusion criteria
* Age \< 18 years or Age \> 75 years * Active bleeding; bleeding diathesis; coagulopathy * Increased risk of bradycardiac events * History of gastrointestinal or genitourinary bleeding \<2 months * Major surgery in the last 6 weeks * History of intracranial bleeding or structural abnormalities * Suspected aortic dissection * Any other condition that may put the patient at risk or influence study results or investigator's opinion (severe hemodynamic instability, known malignancies or other comorbid conditions with life expectancy \<1 year) * Administration in the week before the index event of clopidogrel, ticlopidine, prasugrel, ticagrelor, thrombolytics, bivalirudin, low-molecular weight heparin or fondaparinux . * Concomitant oral or IV therapy with strong CYP3A inhibitors or strong CYP3A inducers, CYP3A with narrow therapeutic windows * Known relevant hematological deviations: Hb \<10 g/dl, Thrombi. \<100x10\^9/l * Use of coumadin derivatives within the last 7 days * Chronic therapy with ticagrelor, prasugrel, clopidogrel or ticlopidine * Known severe liver disease, severe renal failure * Known allergy to the study medications * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual Platelet Reactivity | 1 hour | residual platelet reactivity by Platelet Reactivity Units (PRU) VerifyNow 1 hour after ticagrelor LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High Residual Platelet Reactivity | 1 hour | The percent of patients with a high residual platelet reactivity (PRU \> 208) 1 hour after ticagrelor LD. |
| Bleeding Events | 48 hours | Percentage of participants with Major, minor, minimal bleeding (TIMI criteria) events |
| Dyspnoea and/or Symptomatic Bradycardia | 6 months | Percentage of participants with Occurrence of dyspnoea and/or symptomatic bradycardia |
Countries
Greece, Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor Mashed Pills Ticagrelor loading dose (LD) 180 mg as mashed pills
Ticagrelor mashed pills: The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In all case before the end of the PCI (percutaneous coronary intervention) . In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (90 mg Ticagrelor). Mashed pills administration will be prepared placing 2 ticagrelor pills in a mortar and mashing for 60 seconds using a pestle. The total contents of the mortar will be transferred to the dosing cup, 50 mL of purify water will be added, and the suspension mixed up before drinking. Afterwards, 100 mL of purify water will be administered to the patient. | 41 |
| Ticagrelor Integral Pills Ticagrelor loading dose (LD) 180 mg as integral pills
Ticagrelor integral pills: The loading dose will be performed as soon as possible in the Emergency Room or in the Cath Lab. In all case before the end of the PCI (percutaneous coronary intervention) . In the case of vomit in the first hour after drug loading dose a new reduced loading dose will be administered (90 mg Ticagrelor). | 41 |
| Total | 82 |
Baseline characteristics
| Characteristic | Ticagrelor Integral Pills | Total | Ticagrelor Mashed Pills |
|---|---|---|---|
| Age, Continuous | 61 years STANDARD_DEVIATION 14 | 62 years STANDARD_DEVIATION 13 | 64 years STANDARD_DEVIATION 13 |
| Region of Enrollment Greece | 15 participants | 30 participants | 15 participants |
| Region of Enrollment Italy | 26 participants | 52 participants | 26 participants |
| Sex: Female, Male Female | 8 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Male | 33 Participants | 64 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 41 | 8 / 41 |
| serious Total, serious adverse events | 2 / 41 | 2 / 41 |
Outcome results
Primary
Residual Platelet Reactivity
residual platelet reactivity by Platelet Reactivity Units (PRU) VerifyNow 1 hour after ticagrelor LD.
Time frame: 1 hour
Population: Continuous data were expressed as mean ± standard deviation or medians (quartiles) as appropriate, and categorical data as proportions (%). A P value \< .05 was considered statistically significant. All tests were two-sided.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ticagrelor Mashed Pills | Residual Platelet Reactivity | 168 PRU (P2Y12 reaction units) |
| Ticagrelor Integral Pills | Residual Platelet Reactivity | 252 PRU (P2Y12 reaction units) |
Comparison: Continuous data were expressed as mean ± standard deviation or medians (quartiles) as appropriate, and categorical data as proportions (%). Data were compared by means of the chi-2 test or Fisher exact test for categorical variables and unpaired t test or Mann-Whitney U-test for continuous variables, as appropriate. A P value \< .05 was considered statistically significant. All tests were two-sided.p-value: 0.006t-test, 2 sided
Secondary
Bleeding Events
Percentage of participants with Major, minor, minimal bleeding (TIMI criteria) events
Time frame: 48 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor Mashed Pills | Bleeding Events | 2.4 percentage of partecipants |
| Ticagrelor Integral Pills | Bleeding Events | 7 percentage of partecipants |
Secondary
Dyspnoea and/or Symptomatic Bradycardia
Percentage of participants with Occurrence of dyspnoea and/or symptomatic bradycardia
Time frame: 6 months
Population: Continuous data were expressed as mean ± standard deviation or medians (quartiles) as appropriate, and categorical data as proportions (%)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor Mashed Pills | Dyspnoea and/or Symptomatic Bradycardia | 12 percentage of partecipants |
| Ticagrelor Integral Pills | Dyspnoea and/or Symptomatic Bradycardia | 12 percentage of partecipants |
Secondary
High Residual Platelet Reactivity
The percent of patients with a high residual platelet reactivity (PRU \> 208) 1 hour after ticagrelor LD.
Time frame: 1 hour
Population: Categorical data were expressed as proportions (%)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor Mashed Pills | High Residual Platelet Reactivity | 35 percentage of partecipants |
| Ticagrelor Integral Pills | High Residual Platelet Reactivity | 63 percentage of partecipants |