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

Primary Purpose

STEMI

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Intravenous N-Acetylcysteine

About this trial

This is an interventional treatment trial for STEMI focused on measuring STEMI

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Alberta Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intravenous N-Acetylcysteine arm

Control arm

Arm 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.

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Myocardial salvage

Myocardial salvage as measured by T2-weighted short tau inversion recovery on CMR assessed at 3-5 days after infarction

Left ventricular ejection fraction

Left ventricular ejection fraction on CMR at 3-5 days

ST-segment elevation resolution

ST-segment elevation resolution at 90 minutes after thrombolysis as assessed by the worst lead on electrocardiogram (ECG core lab).

TIMI frame count in infarct related artery

TIMI frame count on baseline coronary angiogram in the infarct-related artery

Creatine kinase MB area under the curve

Creatine kinase MB area under the curve through 24 hours

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

Bleeding

Bleeding research consortium type II, III and V bleeding; safety outcome

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

Full Information

NCT ID

NCT04023266

First Posted

July 9, 2019

Last Updated

October 3, 2022

Sponsor

University of Alberta

1. Study Identification

Unique Protocol Identification Number

NCT04023266

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

September 20, 2019 (Actual)

Primary Completion Date

November 15, 2020 (Actual)

Study Completion Date

January 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Alberta

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

STEMI

Keywords

STEMI

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

Outcomes Assessor

Masking Description

The clinical outcomes assessor reading the cardiac MRI would be blinded to the study arm allotment.

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intravenous N-Acetylcysteine arm

Arm Type

Experimental

Arm Description

Arm Title

Control arm

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Intravenous N-Acetylcysteine

Other Intervention Name(s)

Generic

Intervention Description

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

Primary Outcome Measure Information:

Title

Myocardial infarct size

Description

The primary clinical endpoint will be myocardial infarct size measured by late gadolinium enhancement CMR imaging at 3-5 days from first medical contact.

Time Frame

3-5 days after first medical contact

Title

Feasibility outcomes

Description

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.

Time Frame

Assessed at the end of the study

Secondary Outcome Measure Information:

Title

Myocardial salvage

Description

Myocardial salvage as measured by T2-weighted short tau inversion recovery on CMR assessed at 3-5 days after infarction

Time Frame

3-5 days after infarction

Title

Left ventricular ejection fraction

Description

Left ventricular ejection fraction on CMR at 3-5 days

Time Frame

3-5 days after infarction

Title

ST-segment elevation resolution

Description

ST-segment elevation resolution at 90 minutes after thrombolysis as assessed by the worst lead on electrocardiogram (ECG core lab).

Time Frame

90-minutes after thrombolysis

Title

TIMI frame count in infarct related artery

Description

TIMI frame count on baseline coronary angiogram in the infarct-related artery

Time Frame

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

Title

Creatine kinase MB area under the curve

Description

Creatine kinase MB area under the curve through 24 hours

Time Frame

24 hours after admission

Title

Von Willebrand factor fragmentation

Description

The proportion of Von Willebrand factor multimers in the low, intermediate and high molecular weight form at the time of angiography

Time Frame

At the time of angiography, assessed up to 7 days from admission

Title

Bleeding

Description

Bleeding research consortium type II, III and V bleeding; safety outcome

Time Frame

From time of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 90 days

Title

Allergic reactions

Description

Allergic reactions including hypotension (SBP< 90 mm Hg or a fall in BP >30 mm Hg below baseline), urticaria, flushing, wheezing and/or angioedema

Time Frame

From time of randomization, upto 48 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michelle Graham, MD. FRCPC

Organizational Affiliation

University of Alberta

Official's Role

Study Chair

Facility Information:

Facility Name

University of Alberta Hospital

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 2B7

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Data regarding IPD will be made available on reasonable request

IPD Sharing Time Frame

ON publication of trial the study protocol will be detailed. The ICF has been uploaded on this site.

IPD Sharing Access Criteria

Study protocol will be published

Learn more about this trial

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

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