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

STEMI Clinical Trial

— PANACEA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04023266
• Other study ID #: Pro00087545
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2019
• Est. completion date: January 1, 2022

Study information

• Verified date: July 2022
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 1, 2022
• Est. primary completion date: November 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• ST Elevation Myocardial Infarction
• STEMI

Intervention

Drug:
• Intravenous N-Acetylcysteine
Intravenous N-acetyl cysteine bolus and infusion as described in the experimental arm.

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Left ventricular ejection fraction	Left ventricular ejection fraction on CMR at 3-5 days	3-5 days after infarction
Secondary	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
Secondary	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
Secondary	Creatine kinase MB area under the curve	Creatine kinase MB area under the curve through 24 hours	24 hours after admission
Secondary	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
Secondary	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
Secondary	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