PANDORA: Delirium Prevention After Cardiac Surgery Using IV Acetaminophen to Prevent Postoperative Delirium in Older Cardiac Surgical Patients

Beth Israel Lahey Health

Status and phase: Active, not recruiting; Phase 3

Conditions: Coronary Artery Disease; Delirium; Delirium in Old Age

Treatments: Drug: IV acetaminophen; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04093219

2019-P-000758

R01AG065554 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

This project will study the impact of scheduled administration of IV acetaminophen on the incidence, duration, and severity of postoperative delirium and other important hospital outcomes. Additionally, this trial will evaluate the effects of IV acetaminophen on longer-term postoperative cognitive dysfunction and functional status and develop a biorepository of perioperative samples as a future resource to probe the mechanisms of postoperative delirium.

The investigators propose three specific aims by conducting a randomized, triple-blind clinical trial that enrolls 900 patients 60 years of age or older undergoing cardiac surgery. Through this trial, the investigators will determine the effect of IV acetaminophen on;

1. the incidence, duration, and severity of postoperative delirium,
2. the use of opioids and other rescue analgesics in the first 48 postoperative hours, daily pain scores at rest and exertion, and length of stay in the Intensive Care Unit and overall hospital length of stay
3. longer-term (one, six, 12 months) cognitive, physical, and self-care functional recovery after surgery.

Enrollment: 900 estimated patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ≥ 60 years of age
2. Patients undergoing cardiac surgery [coronary artery bypass grafting (CABG) with or without valve, isolated valve surgery] requiring cardiopulmonary bypass

Exclusion criteria

1. Pre-operative left ventricular ejection fraction (LVEF) < than 30%
2. Emergent procedures
3. Isolated aortic surgery
4. Liver dysfunction (liver enzymes > 3 times the baseline, all patients will have a baseline liver function test information), history and exam suggestive of jaundice
5. Hypersensitivity to the study drugs
6. Active (in the past year) history of alcohol abuse (≥5 drinks per day for men or ≥ 4 drinks per day for women)
7. Any history of alcohol withdrawal or delirium tremens
8. Delirium at baseline
9. Non-English speaking
10. Prisoners
11. Physician Refusal
12. COVID-19 Positive, symptomatic
13. Co-enrollment with non-approved interventional trial

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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900 participants in 2 patient groups, including a placebo group

IV Acetaminophen

Experimental group

Description:

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

Treatment:

Drug: IV acetaminophen

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo