A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in STEMI

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in Patients Undergoing Pharmaco-invasive Reperfusion Early After an ST-segment Elevation Myocardial Infarction

Conditions
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STEMI

Intervention / Treatment
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* Drug: Intravenous N-Acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting with STEMI within 3 hours of symptom onset and satisfying all of the following criteria: Patient age ≥ 18 years Have received thrombolysis, with intend to pursue a pharmaco-invasive reperfusion strategy. Onset of chest pain to reperfusion time of < 3hrs. STEMI involving anterior and/or inferior wall An absence of baseline Q-waves on the initial ECG: The presence of Q waves defined at baseline using the Selvester QRS screening criteria 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: Previous myocardial infarction Known to have moderate to severe LV systolic dysfunction (LV EF< 45%) Known allergy to thrombolytic therapy or NAC Presence of left bundle branch block Cardiogenic shock (defined as systolic blood pressure of < 90mm Hg, for at least 30 minutes, not responsive to fluid resuscitation) Permanent pacemaker or cardioverter defibrillator implanted previously Patients with contra-indications to thrombolytic therapy Patients with loss of consciousness or confusion Patients with known chronic kidney disease (GFR < 30ml/min/m2) or on dialysis Current pregnancy Planned therapy with primary PCI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Investigator-initiated prospective, single-center, double- arm non-blinded randomized controlled trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous N-Acetylcysteine arm<br>On arrival at the recruiting hospital, eligible and consenting STEMI patients randomly allocated to the experimental arm would be administered an intravenous N-Acetylcysteine 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. | Drug: Intravenous N-Acetylcysteine<br>* Intravenous N-acetyl cysteine bolus and infusion as described in the experimental arm.<br>* Other names: Generic;|
| No Intervention: Control arm<br>Patients randomized to this arm would receive no experimental therapies and would continue to receive all standard guideline recommended medical therapies and interventions. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarct size | The primary clinical endpoint will be myocardial infarct size measured by late gadolinium enhancement CMR imaging at 3-5 days from first medical contact. | 3-5 days after first medical contact | 
| Feasibility outcomes | Primary feasibility outcomes would include the rate of recruitment, the number of patients undergoing cardiac MRI within the stipulated time frame, and completeness of the study data collection. | Assessed at the end of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial salvage | Myocardial salvage as measured by T2-weighted short tau inversion recovery on CMR assessed at 3-5 days after infarction | 3-5 days after infarction | 
| Left ventricular ejection fraction | Left ventricular ejection fraction on CMR at 3-5 days | 3-5 days after infarction | 
| ST-segment elevation resolution | ST-segment elevation resolution at 90 minutes after thrombolysis as assessed by the worst lead on electrocardiogram (ECG core lab). | 90-minutes after thrombolysis | 
| TIMI frame count in infarct related artery | TIMI frame count on baseline coronary angiogram in the infarct-related artery | During index coronary angiogram which will be performed within 24 hours of admission | 
| Creatine kinase MB area under the curve | Creatine kinase MB area under the curve through 24 hours | 24 hours after admission | 
| Von Willebrand factor fragmentation | The proportion of Von Willebrand factor multimers in the low, intermediate and high molecular weight form at the time of angiography | At the time of angiography, assessed up to 7 days from admission | 
| Bleeding | Bleeding research consortium type II, III and V bleeding; safety outcome | From time of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 90 days | 
| Allergic reactions | Allergic reactions including hypotension (SBP< 90 mm Hg or a fall in BP >30 mm Hg below baseline), urticaria, flushing, wheezing and/or angioedema | From time of randomization, upto 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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STEMI