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

NCT04023266 | Completed Phase 2 DMC

• 1 other identifier: Pro00087545
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

STEMI

Keywords

STEMI

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Myocardial salvage

  3-5 days after infarction

• Left ventricular ejection fraction

  3-5 days after infarction

• ST-segment elevation resolution

  90-minutes after thrombolysis

• TIMI frame count in infarct related artery

  During index coronary angiogram which will be performed within 24 hours of admission

• Creatine kinase MB area under the curve

  24 hours after admission

Study Arms (2)

Intravenous N-Acetylcysteine arm

EXPERIMENTAL

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

Control arm

NO INTERVENTION

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

Interventions

Intravenous N-Acetylcysteine DRUG

Intravenous N-acetyl cysteine bolus and infusion as described in the experimental arm.

Also known as: Generic

Intravenous N-Acetylcysteine arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Drugs, Generic

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Michelle Graham, MD. FRCPC

  University of Alberta

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The clinical outcomes assessor reading the cardiac MRI would be blinded to the study arm allotment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Investigator-initiated prospective, single-center, double- arm non-blinded randomized controlled trial.

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 17, 2019
• Study Start: September 20, 2019
• Primary Completion: November 15, 2020
• Study Completion: January 1, 2022
• Last Updated: October 6, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: ON publication of trial the study protocol will be detailed. The ICF has been uploaded on this site.
• Access Criteria: Study protocol will be published

Locations

CA (1)