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

University of Alberta

Status and phase: Completed; Phase 2

Conditions: STEMI

Treatments: Drug: Intravenous N-Acetylcysteine

Study type: Interventional

Funder types: Other

Identifiers

NCT04023266

Pro00087545

Details and patient eligibility

About

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.

Full 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.

Enrollment: 44 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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44 participants in 2 patient groups

Intravenous N-Acetylcysteine arm

Experimental group

Description:

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.

Treatment:

Drug: Intravenous N-Acetylcysteine

Control arm

No Intervention group

Description:

Patients randomized to this arm would receive no experimental therapies and would continue to receive all standard guideline recommended medical therapies and interventions.