IV Acetaminophen for Delirium After Cardiac Surgery

(PANDORA Trial)

Not currently recruiting at 10 trial locations

Overseen By Balachundhar Subramaniam, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Liver dysfunction, Alcohol abuse, Delirium, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 2 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether IV acetaminophen, an intravenous form of the common pain reliever, can reduce the risk of delirium—a state of confusion or disorientation—after heart surgery. Delirium is a common and serious issue for older adults following such surgeries, and preventing it could improve recovery. Participants will receive either the actual IV acetaminophen or a placebo, a non-active substance that looks the same. Individuals aged 60 or older, scheduled for certain types of heart surgery like coronary artery bypass grafting, may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that IV acetaminophen is likely to be safe for humans?

Research has shown that IV acetaminophen is generally safe for people. One study found that patients receiving IV acetaminophen experienced significantly less delirium than those given a placebo. Specifically, 10% of patients with IV acetaminophen experienced delirium, compared to 28% with a placebo. Another study involving 120 older patients undergoing heart surgery found that IV acetaminophen reduced delirium by 64%. These results indicate that the treatment is not only effective but also has a good safety record. While no treatment is completely free of side effects, these findings suggest that IV acetaminophen is a promising option for managing postoperative issues like delirium. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for delirium?

Unlike the standard treatments for delirium after cardiac surgery, which often involve a range of medications like antipsychotics and sedatives, IV acetaminophen offers a different approach. This treatment is unique because it uses acetaminophen, a well-known pain reliever, delivered intravenously to potentially reduce inflammation and pain that may contribute to delirium. Researchers are excited because this method might provide a safer, non-sedative option that targets the root causes of delirium and could improve recovery times without the side effects associated with traditional medications.

What evidence suggests that IV acetaminophen might be an effective treatment for postoperative delirium?

Research has shown that IV acetaminophen, which participants in this trial may receive, can significantly reduce the risk of confusion (delirium) after heart surgery. One study found that only 10% of patients who received IV acetaminophen experienced delirium, compared to 28% of those who received a placebo, indicating an 18% reduction in risk. This treatment effectively manages pain, potentially reducing the need for stronger painkillers known as narcotics. Using fewer narcotics is associated with a lower chance of developing delirium. Therefore, IV acetaminophen shows promise in preventing this complication. ^{1 4 6 7 8}

Who Is on the Research Team?

Balachundhar Subramaniam, MD, MPH

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 60 or older who are undergoing certain types of cardiac surgery with cardiopulmonary bypass. It's not suitable for prisoners, COVID-19 positive individuals, those needing urgent procedures, non-English speakers, patients with severe heart or liver issues, a recent history of alcohol abuse, or anyone already experiencing delirium.

Inclusion Criteria

I am 60 years old or older.

I am having heart surgery that needs a heart-lung machine.

Exclusion Criteria

Co-enrollment with non-approved interventional trial

You have regularly consumed a large amount of alcohol in the past year.

You have experienced severe alcohol withdrawal or delirium tremens in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

2 days

In-hospital stay

Postoperative Monitoring

Participants are monitored for incidence, duration, and severity of postoperative delirium and other outcomes

5-6 days

Daily assessments in-hospital

Follow-up

Participants are monitored for cognitive, physical, and functional recovery at 1, 6, and 12 months post-surgery

12 months

Telephonic assessments at 1, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• IV acetaminophen
• Placebo

Trial Overview The PANDORA study is testing whether IV acetaminophen can prevent postoperative delirium—a common complication after cardiac surgery in older patients—compared to a placebo. Participants will be randomly assigned to receive either the drug or placebo.

How Is the Trial Designed?

Group I: IV Acetaminophen Experimental Treatment 1 Intervention

1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively

Group II: Placebo Placebo Group 1 Intervention

Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a pilot study of 12 cardiac surgery patients over 60 years old, the use of intravenous acetaminophen (IVA) significantly reduced the incidence of postoperative delirium to 17%, compared to 67% in those who did not receive IVA.

The study demonstrated feasibility for further research, as all patients completed the study, and suggests that combining IVA with dexmedetomidine may be beneficial in minimizing delirium after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium in cardiac surgery patients over 60 years of age: a pilot study. Susheela, AT., Packiasabapathy, S., Gasangwa, DV., et al.[2020]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30778597/

Effect of Intravenous Acetaminophen vs Placebo ... - PubMed 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/ct2/show/NCT06613178

NCT06613178 | Intravenous Acetaminophen After Cardiac ... Other important secondary outcomes are the total use of narcotics, ICU and hospital stay, improved cognitive function at 6 months and 1 year ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2725234

Effect of Intravenous Acetaminophen vs Placebo ... Mamoun et al previously assessed use of IV acetaminophen every 6 hours for 24 hours following cardiac surgery, in which reduced pain intensity ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06613178/intravenous-acetaminophen-after-cardiac-surgery-definitive-study

Intravenous Acetaminophen After Cardiac Surgery The underlying hypothesis is that better pain control and less use of narcotics will lead to a lower incidence of delirium from day 1 to 7 ...

5. trialx.com trialx.com/clinical-trials/listings/319960/iv-acetaminophen-after-cardiac-surgery-pilot/

IV Acetaminophen After Cardiac Surgery - PILOT The primary endpoint is development of Delirium during the post-operative stay. Description. The study is randomized, double-blinded, and ...

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

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

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05246644?term=ACETAMINOPHEN&viewType=Table&rank=1

NCT05246644 | IV Acetaminophen After Cardiac Surgery Development of delirium post operatively, Incidence of delirium will be analyzed between patients treated with IV or oral acetaminophen , measured from 24 hours ...

8. 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%.