Intravenous Acetaminophen for Delirium After Cardiac Surgery

(IVACS Trial)

Recruiting at 8 trial locations

Overseen By Sheldon Magder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Disqualifiers: Psychiatric treatment, Alzheimer's, Seizure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

1100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intravenous (IV) acetaminophen prevents delirium (confusion) after heart surgery more effectively than the usual oral acetaminophen. Researchers believe that better pain control with less reliance on strong painkillers might reduce delirium and other post-surgery complications. Participants will receive either IV acetaminophen with a placebo oral pill or a placebo IV fluid with real oral acetaminophen. This trial is ideal for those undergoing planned heart surgery, particularly bypass or valve replacement, who are stable before the procedure. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a psychiatric history with current active treatment, you may be excluded from participating.

What is the safety track record for intravenous acetaminophen?

Research has shown that intravenous (IV) acetaminophen, a common pain reliever, is generally safe for people. In a study with 120 older patients who underwent heart surgery, IV acetaminophen reduced the risk of delirium by 64%. Patients experienced fewer instances of delirium, which can occur due to surgery and medication, indicating it was well-tolerated. While this is encouraging, it is important to remember that all medications can have side effects. However, the FDA has already approved IV acetaminophen for pain relief, so its safety is well established. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about intravenous acetaminophen for delirium after cardiac surgery because it offers a new delivery method that could potentially enhance its effectiveness. While traditional treatments for post-surgery delirium often include medications like antipsychotics or sedatives, which can have significant side effects, intravenous acetaminophen is believed to provide pain relief without these drawbacks. This method bypasses the digestive system, allowing for faster and more targeted relief, which is crucial in managing delirium symptoms quickly. Additionally, by reducing pain effectively, it may help minimize the need for opioids, thus reducing the risk of opioid-related complications.

What evidence suggests that intravenous acetaminophen might be an effective treatment for delirium after cardiac surgery?

This trial will compare intravenous acetaminophen with oral acetaminophen for reducing delirium after cardiac surgery. Studies have shown that administering acetaminophen through an IV can effectively reduce confusion and disorientation (delirium) following heart surgery. In one study, patients who received IV acetaminophen had a 10% chance of experiencing delirium, compared to 28% for those who received a placebo, marking a significant reduction of 18%. Further research suggests that IV acetaminophen also helps lower pain and reduces the need for stronger pain medications, which may help decrease delirium. Although some studies did not find a difference in long-term thinking and memory, the immediate reduction in delirium is promising. Overall, strong evidence indicates that IV acetaminophen can reduce delirium shortly after surgery. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals who have undergone cardiac surgery and are experiencing postoperative pain. It aims to see if IV acetaminophen can help prevent delirium from day 1 to 7 after the surgery. Participants should not be using other narcotics that could affect the study's results.

Inclusion Criteria

greater or equal to 18

* elective cardiac surgery

* stable pre-operative

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IV acetaminophen and oral placebo or IV placebo and oral acetaminophen every 6 hours for 48 hours after cardiac surgery

1 week

In-hospital monitoring

Follow-up

Participants are monitored for delirium and other outcomes for up to 7 days post-surgery or until discharge

1 week

In-hospital monitoring

Long-term Follow-up

Cognitive function and opioid use are assessed at 6 months and 1 year post-surgery

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Intravenous Acetaminophen

Trial Overview The study tests whether IV acetaminophen is more effective than oral acetaminophen in preventing delirium following cardiac surgery. The trial also measures narcotic use, length of ICU/hospital stay, cognitive function up to a year post-surgery, and NSAID-related complications.

How Is the Trial Designed?

Group I: Oral Placebo Active Control 1 Intervention

Subject receives active intravenous acetaminophen and oral placebo acetaminophen

Group II: Oral Acetaminophen Placebo Group 1 Intervention

Subject receives placebo IV fluid (saline) and active oral acetaminophen

Intravenous Acetaminophen is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Paracetamol for:

• Pain relief
• Fever reduction

Approved in United States as Tylenol for:

• Pain relief
• Fever reduction

Approved in Canada as Acetaminophen IV for:

• Pain relief
• Fever reduction

Approved in Japan as Paracetamol for:

• Pain relief
• Fever reduction

Approved in China as Paracetamol for:

• Pain relief
• Fever reduction

Approved in Switzerland as Paracetamol for:

• Pain relief
• Fever reduction

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

St. Boniface Hospital

Collaborator

Trials

55

Recruited

15,000+

Sunnybrook Health Sciences Centre

Collaborator

Trials

693

Recruited

1,569,000+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

Trillium Health Centre

Collaborator

Trials

9

Recruited

6,200+

Published Research Related to This Trial

In a study of 141 parturients undergoing elective cesarean delivery, intravenous acetaminophen significantly reduced opioid consumption and pain scores compared to no acetaminophen, highlighting its efficacy in postoperative pain management.

However, intravenous acetaminophen did not show a significant advantage over oral acetaminophen in reducing opioid use or improving other outcomes, suggesting that both forms are effective but intravenous administration may be more beneficial when no acetaminophen is used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous vs Oral Acetaminophen for Analgesia After Cesarean Delivery: A Randomized Trial. Wilson, SH., Wolf, BJ., Robinson, SM., et al.[2020]

A study involving 213 adult inpatients found that intravenous (IV) acetaminophen, administered in doses of either 1,000mg every 6 hours or 650mg every 4 hours for up to 5 days, was safe and well tolerated, with a low incidence of treatment-related adverse events.

Despite a high frequency of adverse events reported due to the patients' comorbidities, only 8% withdrew from the study because of these events, and no significant hepatic issues were linked to IV acetaminophen, supporting its use as a safe pain management option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of multiple-dose intravenous acetaminophen in adult inpatients. Candiotti, KA., Bergese, SD., Viscusi, ER., et al.[2022]

Intravenous (IV) paracetamol is widely used in hospitals for managing fever and pain, and significant adverse reactions are very rare.

However, there is a case report of severe hypotension and cardiac arrest associated with IV paracetamol infusion, highlighting the need for careful monitoring during its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paracetamol infusion-related severe hypotension and cardiac arrest in a child. Yaman, A., Demir, B., Belen, FB., et al.[2018]

This study will investigate the effects of scheduled acetaminophen administration on postoperative delirium in 900 older cardiac surgery patients, aiming to reduce the incidence of delirium and improve long-term cognitive outcomes.

The trial is designed as a multicenter, randomized, placebo-controlled study, with a primary focus on the incidence of in-hospital delirium and secondary outcomes including pain management and lengths of hospital and ICU stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial. Khera, T., Mathur, PA., Banner-Goodspeed, VM., et al.[2021]

A systematic review of 16 studies involving 1,464 patients found that intravenous (IV) acetaminophen is effective for managing acute postoperative pain, showing similar analgesic outcomes compared to active comparators in 7 out of 8 studies.

IV acetaminophen significantly improved pain relief compared to placebo in 12 out of 14 studies, and it was associated with reduced opioid consumption, indicating its potential to enhance pain management while minimizing opioid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A literature review of randomized clinical trials of intravenous acetaminophen (paracetamol) for acute postoperative pain. Macario, A., Royal, MA.[2022]

In the DEXACET trial involving 120 older cardiac surgical patients, intravenous acetaminophen significantly reduced in-hospital delirium compared to placebo, indicating its potential short-term benefits in postoperative care.

However, at 1 and 12 months post-surgery, there were no significant differences in long-term cognitive and functional outcomes between the acetaminophen and placebo groups, suggesting that while it may help with immediate delirium, it does not improve long-term cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twelve-Month Cognitive and Functional Outcomes Following Cardiac Surgery: The DEXACET Trial of Intravenous Acetaminophen Versus Placebo. Khera, T., Helfand, J., Kelly, L., et al.[2022]

This study is investigating the effectiveness of postoperative intravenous acetaminophen combined with either dexmedetomidine or propofol in reducing the incidence of delirium in elderly cardiac surgery patients, with a focus on those aged 60 and older undergoing surgeries like CABG.

The trial is a randomized, placebo-controlled, double-blinded study involving 120 patients, aiming to assess not only delirium incidence but also cognitive decline and other postoperative outcomes, which could lead to improved sedation and analgesia protocols in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. Shankar, P., Mueller, A., Packiasabapathy, S., et al.[2020]

In a study involving 80 children aged 1-12 undergoing cardiac surgery, a single dose of intravenous Paracetamol significantly reduced mean body temperature in the first 24 hours post-operation compared to a placebo.

The incidence of fever was lower in the Paracetamol group, with 42.5% of these patients not requiring additional antipyretic treatment, indicating both efficacy and a favorable safety profile for Paracetamol in managing post-operative fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of preoperative intravenous paracetamol administration on postoperative fever in pediatrics cardiac surgery. Abdollahi, MH., Foruzan-Nia, K., Behjati, M., et al.[2021]

A systematic review of 9 studies found that typical dosing for intravenous paracetamol in term neonates often results in lower than target pain relief concentrations, while investigator-initiated dosing can achieve the desired levels.

For preterm neonates between 32-44 weeks, a recommended dosing regimen is a loading dose of 20 mg/kg followed by 10 mg/kg every 6 hours, which has shown short-term safety, while for those <32 weeks, a loading dose of 12 mg/kg and maintenance of 6 mg/kg every 6 hours is suggested, though further studies are needed for safety confirmation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Paracetamol Dosing Guidelines for Pain Management in (pre)term Neonates Using the Paediatric Study Decision Tree. Mian, P., Knibbe, CAJ., Calvier, EAM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6439609/

Effect of Intravenous Acetaminophen vs Placebo Combined ... Patients treated with IV acetaminophen had a significant reduction in delirium (10% vs 28% placebo; difference, −18% [95% CI, −32% to −5%]; P = ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04093219

PANDORA: Delirium Prevention After Cardiac Surgery ... This project will study the impact of scheduled administration of IV acetaminophen on the incidence, duration, and severity of postoperative delirium.

3. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.803903/full

The DEXACET Trial of Intravenous Acetaminophen Versus ... Administration of intravenous acetaminophen was not associated with a difference in long term cognitive or functional status following cardiac surgery.

4. withpower.com withpower.com/trial/phase-4-postoperative-pain-6-2024-1d3f5

Intravenous Acetaminophen for Delirium After Cardiac ... In the DEXACET trial involving 120 older cardiac surgical patients, intravenous acetaminophen significantly reduced in-hospital delirium compared to placebo, ...

5. epain.org epain.org/journal/view.html?uid=1896&vmd=Full

a systematic review and meta-analysis Although IV AAP reportedly reduced acute postoperative pain scores by 25%–35% and opioid consumption by 40%–50% following cardiac surgery [13], ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7949372/

Scheduled Prophylactic 6-Hourly IV AcetaminopheN to ... This study will provide generalisable evidence for prophylactic efficacy of acetaminophen in reducing the incidence of postoperative delirium in ...

7. bmjopen.bmj.com bmjopen.bmj.com/content/15/5/e097079

Intravenous acetaminophen for postoperative delirium in ... Indeed, a randomised-controlled trial of 120 older patients undergoing cardiac surgery shows that intravenous acetaminophen reduced delirium by 64%.

8. atsjournals.org atsjournals.org/doi/pdf/10.1513/AnnalsATS.202506-683OC?download=true

Role of Acetaminophen in Intensive Care Unit Delirium ... We investigated the impact of excluding cardiac surgical patients, a population in which the efficacy of intravenous acetaminophen has ...

9. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-2718-0

Dexmedetomidine and intravenous acetaminophen for ... - Trials Despite these promising findings, IV acetaminophen has never been studied in the context of delirium prevention following cardiac surgery.