Clinical trial NCT04023266: A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in STEMI
Official title: A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in Patients Undergoing Pharmaco-invasive Reperfusion Early After an ST-segment Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: STEMI
Keywords: STEMI
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2019-07-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated prospective, single-center, double- arm non-blinded randomized controlled trial.
Primary purpose: TREATMENT

Brief summary: The PANACEA trial is an investigator-initiated prospective, single-center, two-arm, non-blinded pilot randomized controlled trial of high-dose IV N-Acetylcysteine therapy used as an adjunct to pharmaco-invasive reperfusion in patients presenting early after a large STEMI.

Detailed description: Patients presenting with ST-segment elevation myocardial infarction within 3 hours of symptom onset and satisfying all of the inclusion criteria after informed consent would be randomly allocated to either intravenous N-Acetylcysteine or standard treatment using a 1:1 allocation ratio. Those randomized to IV N-Acetylcysteine would be administered a bolus of 1200 mg over 0.5 hours (in 5% Dextrose) followed by 600mg/hour for the remaining 47.5 hours (in 5% dextrose). A total N-acetylcysteine dose of 29.7 grams is administered over 48 hours. The infusion is continued during the primary percutaneous coronary intervention. Patients would be followed up for a minimum of 90 days. The primary clinical endpoint will be myocardial infarct size measured by late gadolinium enhancement CMR imaging at 3-5 days from first medical contact. Primary feasibility outcome will be the rate of recruitment, the number of patients undergoing cardiac MRI within the stipulated time frame, and completeness of the study data collection.

Eligibility criteria: Inclusion Criteria:

Patients presenting with STEMI within 3 hours of symptom onset and satisfying all of the following criteria:

1. Patient age ≥ 18 years
2. Have received thrombolysis, with intend to pursue a pharmaco-invasive reperfusion strategy. Onset of chest pain to reperfusion time of \< 3hrs.
3. STEMI involving anterior and/or inferior wall
4. An absence of baseline Q-waves on the initial ECG: The presence of Q waves defined at baseline using the Selvester QRS screening criteria
5. Have a high-risk STEMI ECG defined as:

   * ≥2mm ST-segment elevation in 2 anterior or lateral leads; or
   * ≥2 mm ST-segment elevation in 2 inferior leads coupled with ST-segment depression in 2 contiguous anterior leads for a total ST-segment deviation of ≥4 mm

Exclusion Criteria:

1. Previous myocardial infarction
2. Known to have moderate to severe LV systolic dysfunction (LV EF\< 45%)
3. Known allergy to thrombolytic therapy or NAC
4. Presence of left bundle branch block
5. Cardiogenic shock (defined as systolic blood pressure of \< 90mm Hg, for at least 30 minutes, not responsive to fluid resuscitation)
6. Permanent pacemaker or cardioverter defibrillator implanted previously
7. Patients with contra-indications to thrombolytic therapy
8. Patients with loss of consciousness or confusion
9. Patients with known chronic kidney disease (GFR \< 30ml/min/m2) or on dialysis
10. Current pregnancy
11. Planned therapy with primary PCI

Primary outcomes:
measure: Myocardial infarct size
timeFrame: 3-5 days after first medical contact
measure: Feasibility outcomes
timeFrame: Assessed at the end of the study
Secondary outcomes:
measure: Myocardial salvage
timeFrame: 3-5 days after infarction
measure: Left ventricular ejection fraction
timeFrame: 3-5 days after infarction
measure: ST-segment elevation resolution
timeFrame: 90-minutes after thrombolysis
measure: TIMI frame count in infarct related artery
timeFrame: During index coronary angiogram which will be performed within 24 hours of admission
measure: Creatine kinase MB area under the curve
timeFrame: 24 hours after admission
measure: Von Willebrand factor fragmentation
timeFrame: At the time of angiography, assessed up to 7 days from admission
measure: Bleeding
timeFrame: From time of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 90 days
measure: Allergic reactions
timeFrame: From time of randomization, upto 48 hours
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
affiliation: University of Alberta
name: Michelle Graham, MD. FRCPC
role: STUDY_CHAIR
References: