IV Acetaminophen for Delirium After Cardiac Surgery

(PANDORA Trial)

Recruiting at 9 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

900 Participants Needed

Trial Summary

What is the purpose of this trial?

Our objective is to find an effective prophylactic intervention by evaluating IV acetaminophen's impact in reducing the frequency of postoperative delirium, one of the most common and detrimental complications of cardiac surgery in older adults.

How does the drug IV acetaminophen differ from other treatments for delirium after cardiac surgery?

IV acetaminophen is unique because it is administered directly into the bloodstream, which can provide faster relief compared to oral medications. It has been shown to reduce the incidence of delirium after cardiac surgery, potentially by decreasing the need for opioids, which are known to contribute to delirium. ^{1 2 3 4}

Research Team

Balachundhar Subramaniam, MD, MPH

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England 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. [2020]

2. England 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. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Twelve-Month Cognitive and Functional Outcomes Following Cardiac Surgery: The DEXACET Trial of Intravenous Acetaminophen Versus Placebo. [2022]

4. England 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. [2020]