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The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor (ON-TIME 3)

Primary Purpose

STEMI, STEMI - ST Elevation Myocardial Infarction

Status

Completed

Phase

Phase 4

Locations

Netherlands

Study Type

Interventional

Intervention

Paracetamol

Fentanyl

About this trial

This is an interventional treatment trial for STEMI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

i. age ≥18 years

ii. referred by ambulance paramedics to Isala (Zwolle) or Zuyderland Hospital (Heerlen)

iii. diagnosed in the ambulance with STEMI defined as:

ongoing chest pain >30 minutes and <12 hours duration and
ST-segment elevation >0.1 milliVolt in at least 2 contiguous leads

iv. ongoing chest pain with a pain score (NRS) ≥4

v. the patient has been informed of the nature of the study, agrees to its provisions and has provided verbal informed consent in the pre-hospital phase followed by written informed consent in hospital

Exclusion Criteria:

i. presenting with cardiogenic shock; defined as:

systolic blood pressure <90 mmHg and
heart rate >100/min and
peripheral oxygen saturation <90% (without oxygen administration)

ii. patients with a nasogastric tube in situ or requiring a nasogastric tube

iii. patients who already received fentanyl or paracetamol <2 hours prior to randomization

iv. patients on current treatment with P2Y12 inhibitors (ticagrelor, clopidogrel or prasugrel)

v. allergy to morphine or paracetamol

vi. patients with recent major bleeding complications or contraindication to dual antiplatelet therapy:

hypersensitivity to aspirin or ticagrelor
current use of (new) oral anticoagulation
history of bleeding diathesis or known coagulopathy
active bleeding
refusal of blood transfusions
history of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke
known severe liver dysfunction

vii. received any organ transplant or is on a waiting list for any organ transplant

viii. patients undergoing dialysis

ix. pregnant or lactating female

x. patients currently participating in another investigational drug or device study

Sites / Locations

Isala clinics

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

paracetamol

fentanyl

Arm Description

Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.

Outcomes

Primary Outcome Measures

platelet reactivity

Platelet reactivity units (PRU) directly post-PCI or 1 hour post-angiography

Secondary Outcome Measures

Full Information

NCT ID

NCT03400267

First Posted

October 30, 2017

Last Updated

February 11, 2020

Sponsor

A.H. Tavenier

Collaborators

Isala

1. Study Identification

Unique Protocol Identification Number

NCT03400267

Brief Title

The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor

Acronym

ON-TIME 3

Official Title

The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

February 16, 2018 (Actual)

Primary Completion Date

October 22, 2019 (Actual)

Study Completion Date

November 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

A.H. Tavenier

Collaborators

Isala

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Fast and accurate platelet inhibition is an important therapeutic goal in the acute treatment of patients with ST-segment elevation myocardial infarction (STEMI). Platelet inhibitory effects induced by normal oral P2Y12 receptor antagonists, for example ticagrelor, are delayed in STEMI patients undergoing primary percutaneous coronary intervention (primary PCI), which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). Another therapeutic goal in the acute treatment of STEMI is reduction of sympathetic stress and catecholamine release, thereby improving the balance between the demand for and supply of oxygen, by analgesia like fentanyl of morphine. To date, there are no studies that have specifically assessed the pharmacodynamics influences of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor tablets. Therefore, In the ON-TIME-3 study, the investigators seek to show the influence of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed ticagrelor in the ambulance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

STEMI, STEMI - ST Elevation Myocardial Infarction

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

randomized controlled trial, with randomization to either paracetamol intravenously or fentanyl.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Actual)

8. Arms, Groups, and Interventions

Arm Title

paracetamol

Arm Type

Active Comparator

Arm Description

Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.

Arm Title

fentanyl

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

Paracetamol

Intervention Description

Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.

Intervention Type

Drug

Intervention Name(s)

Fentanyl

Intervention Description

Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.

Primary Outcome Measure Information:

Title

platelet reactivity

Description

Platelet reactivity units (PRU) directly post-PCI or 1 hour post-angiography

Time Frame

directly post-PCI or 1 hour post-angiography

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: i. age ≥18 years ii. referred by ambulance paramedics to Isala (Zwolle) or Zuyderland Hospital (Heerlen) iii. diagnosed in the ambulance with STEMI defined as: ongoing chest pain >30 minutes and <12 hours duration and ST-segment elevation >0.1 milliVolt in at least 2 contiguous leads iv. ongoing chest pain with a pain score (NRS) ≥4 v. the patient has been informed of the nature of the study, agrees to its provisions and has provided verbal informed consent in the pre-hospital phase followed by written informed consent in hospital Exclusion Criteria: i. presenting with cardiogenic shock; defined as: systolic blood pressure <90 mmHg and heart rate >100/min and peripheral oxygen saturation <90% (without oxygen administration) ii. patients with a nasogastric tube in situ or requiring a nasogastric tube iii. patients who already received fentanyl or paracetamol <2 hours prior to randomization iv. patients on current treatment with P2Y12 inhibitors (ticagrelor, clopidogrel or prasugrel) v. allergy to morphine or paracetamol vi. patients with recent major bleeding complications or contraindication to dual antiplatelet therapy: hypersensitivity to aspirin or ticagrelor current use of (new) oral anticoagulation history of bleeding diathesis or known coagulopathy active bleeding refusal of blood transfusions history of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke known severe liver dysfunction vii. received any organ transplant or is on a waiting list for any organ transplant viii. patients undergoing dialysis ix. pregnant or lactating female x. patients currently participating in another investigational drug or device study

Facility Information:

Facility Name

Isala clinics

City

Zwolle

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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The Effect of Opioids on P2Y12 Receptor Inhibition in Patients With ST-Elevation Myocardial Infarction Who Are Pre-treated With Crushed Ticagrelor

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