No registrations found.
ID
Source
Brief title
Health condition
STEMI
PCI
P2Y12 receptor antagonists
platelet inhibition
Fantanyl
Paracetamol
Ambulance
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is to show that patients with STEMI who are pre-treated with crushed ticagrelor 180 mg and paracetamol 1000 mg have a higher level of platelet inhibition directly after primary PCI compared to patients pre-treated with crushed ticagrelor 180 mg and fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg. This is measured by the level of platelet reactivity units (PRU) at T2 (directly post-PCI or 1 hour post-angiography.
Secondary outcome
Secondary endpoints:
- Pain reduction measured by the level of
pain using numeric rating score.
- The level of platelet inhibition (PRU) at T1,
T3 and T4.
- The percentage of High on treatment
Platelet Reactivity (HPR) as defined as a
PRU >208 (1) at T1, T2, T3 and T4.
- The level of the active metabolite of a
higher active metabolite of ticagrelor and
AR-C124910XX measured in plasma, at T1,
T2, T3 and T4.
- Extent of ST-segment deviation (¡Ý70% ST-
segment resolution) pre-PCI and 1 hour
post-PCI.
- TIMI flow grade 3 in the culprit vessel
at initial angiography.
- Requiring of fentanyl in patients
randomized to paracetamol.
- MACE and stent thrombosis at 30 days of
follow-up.
Background summary
Background of the study:
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 PD influences of fentanyl on platelet inhibition in STEMI patients who are pre-treated with crushed
ticagrelor tablets. Therefore, In the ON-TIME-3 study, we seek to show the influence of fentanyl on platelet inhibition in STEMI
patients who are pre-treated with crushed ticagrelor in the ambulance.
Objective of the study:
Primary Objective: The aim of the study is to show that STEMI patients who are pre-treated with crushed ticagrelor and
paracetamol have a higher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor who are
treated with fentanyl.
Study design:
This is a multicenter, prospective, randomized, investigator-initiated open-label study
Study population:
Patients with ongoing chest pain with the diagnosis of STEMI in the ambulance.
Intervention:
Patients are randomized to paracetamol 1000mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.
Primary study parameters/outcome of the study:
The primary endpoint of the study is:
to show that patients with STEMI who are pre-treated with crushed ticagrelor 180 mg and paracetamol 1000 mg have a higher
level of platelet inhibition directly after primary PCI compared to patients pre-treated with crushed ticagrelor 180 mg and fentanyl
1-2 mcg/kg with a maximum of 4 mcg/kg.
Study objective
The hypothesis is that STEMI patients who are pre-treated with crushed ticagrelor and paracetamol have a higher level of platelet inhibition after primary PCI than patients pre-treated with crushed ticagrelor who are treated with fentanyl.
Study design
Blood sample measurements for platelet function testing and level of active metabolite of ticagrelor, using Verify Now P2Y12 assay (Accumetrics, San Diego, California), will be done at four time points:
- 1: when arriving at the cathlab
- 2: directly post-primary PCI or 1 hour after
coronary angiography when no PCI was
performed
- 3: one hour post-primary PCI including
electrocardiogram (ECG) or 2 hours post- coronary angiography
- 4: six hours post-primary PCI of 7 hours
post-coronary angiography
Intervention
Patients are randomized to paracetamol 1000 mg iv or fentanyl 1-2 mcg/kg with a maximum of 4 mcg/kg iv.
Dokter Stolteweg 96
Zwolle 8025 AZ
The Netherlands
038-4262999
H.vd.wetering@diagram-zwolle.nl
Dokter Stolteweg 96
Zwolle 8025 AZ
The Netherlands
038-4262999
H.vd.wetering@diagram-zwolle.nl
Inclusion criteria
1. age >17 years
2. referred by ambulance paramedics to Isala
(Zwolle) or Zuyderland Hospital (Heerlen)
3. diagnosed in the ambulance with STEMI
defined as:
- ongoing chest pain >30 minutes and <12
hours duration and
- ST-segment elevation >0.1 mV in at least
2 contiguous leads
4. ongoing chest pain with a pain score (NRS)
¡Ý4
5. 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
1. presenting with cardiogenic shock; defined
as:
- systolic blood pressure <90 mmHg and
- heart rate >100/min and
- peripheral oxygen saturation <90%
(without oxygen administration)
2. patients with a nasogastric tube in situ or
requiring a nasogastric tube
3. patients who already received fentanyl or
paracetamol <2 hours prior to
randomization
4. patients on current treatment with P2Y12
inhibitors
(ticagrelor, clopidogrel or prasugrel)
5. allergy to morphine or paracetamol
6. 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
- refusal of blood transfusions
- history of intracerebral mass, aneurysm,
arteriovenous malformation, or
hemorrhagic stroke
- known severe liver dysfunction
7. received any organ transplant or is on a
waiting list for any organ transplant
8. patients undergoing dialysis
9. pregnant or lactating female
10. patients currently participating in another
investigational drug or device study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6603 |
| NTR-old | NTR6785 |
| Other | : (CCMO) ABR 62462 NL62462.075.17 |