Trial of Caldolor for Treatment of Pain in Post-Operative Adult Patients

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial of Ibuprofen Injection (IVIb) for Treatment of Pain in the Post-Operative Adult Patients

The primary objective of this study of Caldolor (IV ibuprofen) administered to post-operative hospitalized adult patients every 6 hours for 48 hours is to determine the efficacy of Caldolor compared to placebo for the treatment of post-operative pain as measured by reduction in the requirement for the narcotic analgesic, morphine, post surgery

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Intravenous ibuprofen; Other: Normal saline as placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 319
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Cooper Green Hospital / Jefferson Clinic
    • Birmingham, Alabama, United States, 35235
      • Medical Center East / Alabama Clinical Therapeutics
    • Mobile, Alabama, United States, 36608
      • Springhill Hospital / Wilmax Clinical Research, Inc.
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center / Wilmax Clinical Research, Inc.
    • Montgomery, Alabama, United States, 36106
      • Jackson Hospital / Drug Research and Analysis Corporation
    • Montgomery, Alabama, United States, 36111
      • Baptist Medical Center South / Drug Research and Analysis Corporation
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • California
    • Colton, California, United States, 92324
      • Valley OB/GYN
  • Kansas
    • Wichita, Kansas, United States, 67208
      • Research Support Personnel LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Chandler Medical Center; Ken Muse Research
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Comprehensive Pain Specialists
  • Texas
    • Fort Worth, Texas, United States, 76135
      • Health First Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Scheduled for elective abdominal hysterectomy surgery with anticipated need for post-operative I.V. morphine analgesia with anticipated use of ≥ 24 hours.
2. Adequate IV access
3. Anticipated hospital stay ≥ 24 hours

Exclusion Criteria:

1. Be unable to make a reliable self-report of pain intensity to pain relief
2. Less than 18 years of age
3. Greater than 70 years of age
4. Use of NSAIDs within 12 hours prior to dosing
5. Use of analgesics, muscle relaxants and sedatives less than 24 hours prior to CTM administration with the following exceptions: paracetamol (acetaminophen) can be administered until 6 hours prior to surgery; tramadol can be administered until midnight the evening prior to surgery; muscle relaxants working at the neuromuscular junction used for intubation and/or anesthesia administration for the surgical procedure prior to CTM administration; and sedatives (i.e., midazolam) used as a co-induction agent for the surgical procedure prior to CTM administration
6. Patients taking warfarin, lithium, combination of ACE-inhibitors and furosemide
7. Patients with anemia (active clinically significant) and/or a history or evidence of asthma or heart failure
8. History of allergy or hypersensitivity to any component of Caldolor, aspirin (or aspirin related products), NSAIDs, or COX-2 inhibitors
9. Pregnant or nursing
10. History of severe head trauma that required current hospitalization, intracranial surgery or stroke within the previous 30 days, or any history of intracerebral arteriovenous malformation, cerebral aneurysm or CNS mass lesion
11. Weigh less than 30kg
12. Have a history of congenital bleeding diathesis (eg hemophilia) or any active clinically significant bleeding, or have underlying platelet dysfunction including (but not limited to) idiopathic thrombocytopenic purpura, disseminated intravascular coagulation, or congenital platelet dysfunction
13. Have GI bleeding that required medical intervention within the previous 6 weeks (unless definitive surgery has been performed)
14. Have a platelet count less than 30,000mm3 determined within the 28 days prior to surgery
15. Pre-existing dependence on narcotics or known tolerance to opioids
16. Inability to understand the requirements of the study, be willing to provide written informed consent (as evidenced by signature on an informed consent document approved by an Institutional Review Board [IRB]), and agree to abide by the study restrictions and to return for the required assessments
17. Refusal to provide written authorization for use and disclosure of protected health information
18. Be on dialysis, have oliguria or calculated creatinine clearance of less than 60 mL/min (calculated using the Cockcroft and Gault formula) determined within the 28 days prior to surgery
19. Inability to achieve hemostasis or inability to close surgical incision, prior to Operating Room discharge
20. Operative procedure includes organ transplant
21. Pre or intra-operative procedure utilized for the prevention of pre- or post-operative pain (i.e. epidural or nerve blocks)
22. Be receiving full dose anticoagulation therapy or Activated Protein C within 6 hours before dosing (Prophylaxis with subcutaneous heparin is acceptable)
23. Have received another investigational drug within the past 30 days
24. Be otherwise unsuitable for the study in the opinion of the investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: normal saline	Other: Normal saline as placebo comparator; 250 ml normal saline as a placebo comparator was administered every 6 hours for a total of eight doses over the first 48 hours. Those patients who received the initial eight doses could continue to receive additional doses as needed through the end of the treatment period (day 5); Other Names: NS
Active Comparator: intravenous ibuprofen	Drug: Intravenous ibuprofen; 800 mg intravenous ibuprofen diluted in 250 milliliters of normal saline was administered every 6 hours for a total of eight doses over the first 48 hours. Those patients who received the initial eight doses could continue to receive additional doses as needed through the end of the treatment period (day 5); Other Names: Caldolor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Patient Demand for the Narcotic Analgesic, Morphine, Post Surgery	Change in the amount of morphine use (in milligrams) by subjects in each treatment group for a 24 hour period post-surgery	24 Hours

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals

Publications and helpful links

General Publications

• Southworth S, Peters J, Rock A, Pavliv L. A multicenter, randomized, double-blind, placebo-controlled trial of intravenous ibuprofen 400 and 800 mg every 6 hours in the management of postoperative pain. Clin Ther. 2009 Sep;31(9):1922-35. doi: 10.1016/j.clinthera.2009.08.026.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: September 22, 2005
• First Submitted That Met QC Criteria: September 22, 2005
• First Posted (Estimate): September 26, 2005

Study Record Updates

• Last Update Posted (Estimate): June 22, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: CPI-CL-008