IV Acetaminophen for Delirium After Cardiac Surgery
(PANDORA Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Overseen byBalachundhar Subramaniam, MD, MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Beth Israel Deaconess Medical Center
Disqualifiers: Liver dysfunction, Alcohol abuse, Delirium, others
Pivotal Trial (Near Approval)
Prior Safety Data
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.
1234Eligibility 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.
+10 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: IV AcetaminophenExperimental Treatment1 Intervention
1 g IV acetaminophen every 6 hours for 48 hours during the first 2 days postoperatively
Group II: PlaceboPlacebo Group1 Intervention
Volume of the placebo (saline) will match that of IV acetaminophen at 100ml 0.9% NaCl
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Albert Einstein College of Medicine- MontefioreBronx, NY
Beth Israel Deaconess Medical CenterBoston, MA
University of Pittsburgh Medical CenterPittsburgh, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Beth Israel Deaconess Medical CenterLead Sponsor
National Institute on Aging (NIA)Collaborator
References
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]Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and obtain effect size estimates for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited for the study after IRB approval and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who successfully completed the study. Results: All patients completed the study protocol successfully. The total incidence of delirium in the study population was 42% (5/12):  67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in  D+A group and 0%(0/3)  P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension with systolic blood pressure <90 mm of Hg. Conclusions: The feasibility of performing a large-scale project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.
Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial. [2021]Postoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored.
Twelve-Month Cognitive and Functional Outcomes Following Cardiac Surgery: The DEXACET Trial of Intravenous Acetaminophen Versus Placebo. [2022]Background: Delirium, an acute decline in attention and global cognitive dysfunction, occurs frequently following cardiac surgery and has been demonstrated to be significantly associated with cognitive dysfunction and reduced functional ability. In the DEXACET trial, we demonstrated a significant reduction in postoperative in-hospital delirium with intravenous (IV) acetaminophen when compared with placebo. In this analysis we examined whether this protective association also extended to 12 month cognitive and functional outcomes. Methods: This study was a prospective, randomized, placebo-controlled, triple-blinded, factorial design trial conducted at Beth Israel Deaconess Medical Center, approved by the IRB. In this trial, 120 older cardiac surgical patients were randomly assigned to receive either intravenous (IV) acetaminophen or placebo in addition to propofol or dexmedetomidine. Those receiving IV acetaminophen displayed a significant reduction in in-hospital delirium. We collected cognitive, mood and functional outcome data using the Montreal Cognitive Assessment, telephone version (T-MoCA), Geriatric Depression Scale (GDS) and the Basic and Instrumental Activities of Daily Living (ADLs, IADLs) at 1 month and 12 months after surgery. Results: Of the 120 enrolled patients in the primary trial, 93 (77.5%) and 83 (69.2%) patients responded to assessments at 1 month and 12 months, respectively. No statistically significant differences in median T-MoCA scores were observed between acetaminophen and placebo groups at 1 month (18.0 vs.18.0, p = 0.52) or 12 months (19.0 vs.18.0, p = 0.62) following surgery. There were similarly no differences in GDS, ADLs or IADLs between treatment groups. Losses to follow-up limited the sample sizes and 10 of the 23 (45%) original study participants who had postoperative delirium were lost to follow up. Conclusion: Administration of intravenous acetaminophen was not associated with a difference in long term cognitive or functional status following cardiac surgery. Additional research on long-term outcomes following postoperative delirium with a larger sample size and improved cohort retention strategies will be needed to address this important area.
Dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium following cardiac surgery (DEXACET trial): protocol for a prospective randomized controlled trial. [2020]Postoperative delirium is common in elderly cardiac surgery patients. It is multifactorial and is influenced by the patient's baseline status and the nature of the medical and surgical interventions that the patient receives. Some of these factors are potentially modifiable, including postoperative sedation and analgesia protocols. This study has been designed to evaluate the effectiveness of postoperative intravenous acetaminophen in conjunction with either dexmedetomidine or propofol in decreasing the incidence of delirium.