Effect of Intravenous Ibuprofen on Inflammatory Responses in Patients Undergoing Surgery With General Anesthesia.

Randomized, Double-blind, Pilot Study on the Effect of Intravenous Ibuprofen on Inflammatory Responses in Patients Undergoing Surgery With General Anesthesia: Correlation With Clinical Outcomes

The administration of anti-inflammatory drugs such as ibuprofen before and after surgery has not been studied extensively. Subjects are being asked to participate in this study because they are scheduled for surgery and because the investigators want to study ways to improve recovery from surgery. Ibuprofen will be given several times before and after surgery. The investigators will ask questions to determine recovery and the investigators will draw blood to determine inflammatory response.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Response
• Intervention / Treatment: Drug: Ibuprofen; Drug: Placebo/Saline solution

Detailed Description

Human and animal studies suggest cyclooxygenase-inhibitors (COX-inhibitors) decrease the production of inflammatory mediators. Studies also suggest that COX inhibitors attenuate increases in corticosterone and eicosanoid levels after endotoxin injection. COX inhibitors also appear to have anticancer effects, inhibiting angiogenesis, tumor growth, and metastatic burden. These results suggest a role for IV ibuprofen in preventing untoward inflammatory responses, shortening post-surgical convalescence, improving patient satisfaction, and reducing the rate of complications occurring during the recovery from surgery. However, there are no studies that have evaluated the relationship between administration of IV ibuprofen, ensuing immunomodulation, and long-term outcomes.

Study Objective. The aim of the proposed study is to examine the effect of intravenous(IV) ibuprofen on the inflammatory response in major surgery. More importantly, the investigators will correlate changes in the concentration of inflammatory mediators with meaningful clinical outcomes.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11215
      • NY Methodist Hospital
    • New York, New York, United States, 10016
      • NYU Langone Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults, 18 and over, who will undergo surgery lasting longer than one hour with general anesthesia

2. Subject is non-lactating and is either:

   • Not of childbearing potential
   • Of childbearing potential but is not pregnant at time of baseline as determined by pre-surgical pregnancy testing.
3. Subject is ASA physical status 1, 2, or 3

Exclusion Criteria:

1. Cognitively impaired (by history)
2. Subject requires chronic antipsychotic history
3. Subject is anticipated to require an additional surgery within 90 days after the intended surgery
4. Chronic use of steroids or opioids
5. Subject has received treatment with COX inhibitors within 3 days of study entry
6. Subject for whom opiates, benzodiazepines, and COX inhibitors are contraindicated

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ibuprofen; Eligible subjects will be randomized to one of the two treatment group in a 1:1 ratio to receive either IV ibuprofen or matching placebo.	Drug: Ibuprofen; Patients will receive either 800mg IV ibuprofen or placebo pre-operatively. Post-operatively, patients will receive either 800mg IV ibuprofen or placebo 6 hours after the first dose.; Other Names: nonsteroidal anti-inflammatory drug (NSAID)
Placebo Comparator: Placebo/Saline solution; Eligible subjects will be randomized to one of the two treatment group in a 1:1 ratio to receive either IV ibuprofen or matching placebo	Drug: Placebo/Saline solution; Patients will receive placebo pre-operatively. Post-operatively, patients will receive placebo at least 6 hours after the initial dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentrations of the Cytokines Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin IL-1Beta (IL-1Beta), IL-2, IL-6, IL-10, and Interferon-gamma (IFN-gamma) as Well as Prostaglandin E2 at Different Time Points.	Concentration of the cytokines TNF-alpha, IL-1Beta, IL-2, IL-6, IL-10, and IFN-gamma as well as prostaglandin E2 at different time points will be our primary outcome. Changes in mediator levels in the IV ibuprofen versus placebo groups will be compared. Plasma samples will be collected before administration of any drug (after placement of IV lines), at the end of the surgery, and on the first postoperative day.	48h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery Score (QoR-40).	The secondary outcome parameters will be the quality of recovery score (QoR-40) to measure quality of recovery from surgery, a simple fatigue scale, digits forward and backward, and the global depression schedule. Forty questions in five dimensions will be scored by patients on a five-point Likert scale. Seven point fatigue scales (in- and out-patient) is often used to assess progress of recovery in head trauma patients. Metrics will be administered on at the baseline visit and or on the day of surgery and on postoperative days 1, 2, 4 and 6.	48h

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Lisa Doan, MD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: June 17, 2011
• First Submitted That Met QC Criteria: June 20, 2011
• First Posted (Estimate): June 21, 2011

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: November 24, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Recovery; Cytokines; Ibuprofen; major surgery; IV ibuprofen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Cyclooxygenase Inhibitors; Anti-Inflammatory Agents; Ibuprofen; Anti-Inflammatory Agents, Non-Steroidal
• Other Study ID Numbers: 11-01188

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes