Acetaminophen in aSAH to Inhibit Lipid Peroxidation and Cerebral Vasospasm

NCT00585559 | Terminated Phase 3 Results DMC

• 3 other identifiers: NIH P50 GM015431VUMCIRB060556P50GM015431
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine whether acetaminophen (APAP), N-acetylcysteine (NAC), and APAP in combination with NAC will inhibit lipid peroxidation in aneurysmal subarachnoid hemorrhage (aSAH), utilizing F2-IsoPs as biomarkers for lipid peroxidation.

Conditions

Aneurysmal Subarachnoid Hemorrhage; Cerebral Vasospasm

Keywords

Lipid; Peroxidation; N-Acetylcysteine; Acetaminophen; Vasospasm

Outcome Measures

Primary Outcomes (6)

• Number of Patients With Vasospasm Based on Magnetic Resonance Angiography (MRA)

  Presence of vasospasm measured Magnetic Resonance Angiography (MRA). MRA measures the degree of arterial narrowing, with a higher score indicating more severe vasospasm. An MRA score of 84% sensitivity and 72% specificity is indicative of vasospasm.

  8 Days post subarachnoid hemorrhage (SAH) event

• Number of Patients With Vasospasm Based on Computed Tomographic Angiography (CTA)

  Presence of vasospasm measured by Computed Tomographic Angiography (CTA). CTA scores range from 0 (no vasospasm) to 34, where a score of 10 or more is indicative of vasospasm.

  8 Days post subarachnoid hemorrhage (SAH) event

• National Institutes of Health Stroke Scale (NIHSS) Score

  The scale measures the severity of symptoms associated with patient's stroke. It assesses the severity of impairments related to stroke. The impairments are graded on a 3-4 point scale with scores that range from 0-42. Patients with a higher score have a more severe impairment, and patients with a lower score have a less severe impairment.

  8 Days post subarachnoid hemorrhage (SAH) event

• Modified Rankin Scale (MRS) Score

  The modified Rankin Scale (mRS) is used for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The 7 point ordinal scale ranges from No symptoms (0) to Death (6), with higher scores representing worse outcome.

  8 Days post subarachnoid hemorrhage (SAH) event

• Glasgow Outcome Scale (GOS) Score

  The Glasgow Outcome Scale (GOS) is a scale used to assess recovery of participants with brain damage. The scale has 5 categories: Death (1), Persistent vegetative state (2), Severe disability (3), Moderate disability (4), Good recovery (5).

  8 Days post subarachnoid hemorrhage (SAH) event

• The Barthel Index Score

  The Barthel index measures the extent to which someone can function independently during basic activities of daily living. Scores range from (from 0 to 100), 0 meaning disability and 100 meaning independence, therefore, higher score, better outcome.

  8 Days post subarachnoid hemorrhage (SAH) event

Study Arms (5)

Placebos for acetaminophen and N-acetylcysteine

PLACEBO COMPARATOR

Placebos for acetaminophen and N-acetylcysteine

Drug: Placebos for acetaminophen and N-acetylcysteine

Acetaminophen and N-acetylcysteine placebo

ACTIVE COMPARATOR

Acetaminophen 1 gm every 6 hours and N-acetylcysteine placebo

Drug: APAP 1 gm every 6 hours and N-acetylcysteine placebo

N-acetylcysteine and acetaminophen

ACTIVE COMPARATOR

N-acetylcysteine IV infusion at 0.5 gm hourly and acetaminophen placebo

Drug: NAC IV infusion at 0.5 gm hourly and APAP placebo

Acetaminophen 1 Gram and N-acetylcysteine

ACTIVE COMPARATOR

Acetaminophen 1 gm every 6 hours, plus N-acetylcysteine IV infusion at 0.5 gm hourly

Drug: APAP 1 gm q6 hours, plus NAC IV infusion at 0.5 gm hourly

Acetaminophen 1.5 Gram and N-acetylcysteine

ACTIVE COMPARATOR

Acetaminophen 1.5 gm every 6 hours, plus N-acetylcysteine IV infusion at 0.5 gm hourly

Drug: APAP 1.5 gm q6 hours, plus NAC IV infusion at 0.5 gm hourly

Interventions

Placebos for acetaminophen and N-acetylcysteine DRUG

Placebos for acetaminophen and N-acetylcysteine

Placebos for acetaminophen and N-acetylcysteine

APAP 1 gm every 6 hours and N-acetylcysteine placebo DRUG

Acetaminophen 1 gm every 6 hours and N-acetylcysteine placebo

Acetaminophen and N-acetylcysteine placebo

NAC IV infusion at 0.5 gm hourly and APAP placebo DRUG

N-acetylcysteine IV infusion at 0.5 gm hourly and acetaminophen placebo

N-acetylcysteine and acetaminophen

APAP 1 gm q6 hours, plus NAC IV infusion at 0.5 gm hourly DRUG

Acetaminophen 1 gm every 6 hours, plus N-acetylcysteine IV infusion at 0.5 gm hourly

Acetaminophen 1 Gram and N-acetylcysteine

APAP 1.5 gm q6 hours, plus NAC IV infusion at 0.5 gm hourly DRUG

Acetaminophen 1.5 gm every 6 hours, plus N-acetylcysteine IV infusion at 0.5 gm hourly

Acetaminophen 1.5 Gram and N-acetylcysteine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages ≥ 20
• Fisher Grade III or III + IV SAH based upon admitting CT scan
• Aneurysm secured by either clipping or coiling within 72 hours of SAH
• Intracranial aneurysm confirmed by angiography or CTA
• Presence of ventriculostomy for external ventricular drainage (EVD) prior to randomization

You may not qualify if:

• Consent unobtainable
• Enrollment in another interventional study
• Patient is pregnant or lactating
• Known co-morbidities that could affect outcome of this study
• Contraindication to CTA
• Serum creatinine \> 1.4
• Documented allergy to iodinated contrast that cannot be adequately treated with premedication
• Documented allergy and/or intolerance to ApAP
• Baseline liver disease
• History of recent alcohol abuse with documented ALT or AST above normal laboratory values
• Documented history of both malnutrition and decreased serum albumin below normal lab values
• Documented abnormal platelet count below normal lab values
• Documented abnormal PT or PTT above normal lab values
• History or evidence of active asthma
• Documented allergy and/or intolerance to N-acetylcysteine

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

Interventions

Acetaminophen; Acetylcysteine

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The original trial had multiple stops and starts in enrollment due to PI relocation and funding gaps. This prolonged the patient enrollment periods. Further, the original PI unexpectedly passed away quite suddenly at which point the data management and supervision of the trial reporting passed to its current reporting physician.

Results Point of Contact

• Title: Dr. Matthew Fusco
• Organization: Vanderbilt University Medical Center

matthew.r.fusco@vumc.org

615-322-1054

Study Officials

• Matthew Fusco, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 3, 2008
• Study Start: April 1, 2007
• Primary Completion: October 26, 2023
• Study Completion: October 26, 2023
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)