Efficacy and Safety Study of Caldolor (IV Ibuprofen) in Hospitalized Adult Orthopedic Patients

A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF IBUPROFEN INJECTION (IVIb) FOR TREATMENT OF PAIN IN POST-OPERATIVE ORTHOPEDIC ADULT PATIENTS

The primary objective of this study of Caldolor (IV ibuprofen) administered to post-operative hospitalized adult orthopedic patients every 6 hours for at least 24 hours is to determine the efficacy of Caldolor (IV ibuprofen) compared to placebo for the treatment of post-operative pain by patients self-assessment of pain.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Other: Normal Saline; Drug: Caldolor

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Johannesburg, South Africa
    • Johannesburg General Hospital
  • Krugersdorp, South Africa
    • Krugersdorp Private Hospital
  • Pretoria, South Africa
    • Eugene Marais Hospital
• United States
  • Alabama
    • Mobile, Alabama, United States, 336608
      • Wilmax Clinical Research Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Teton Research, LLC
  • California
    • Arcadia, California, United States, 91007
      • Clinical Management Services, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30350
      • Southeastern Center for Clinical Trials
  • Texas
    • Houston, Texas, United States, 77054
      • Research Concepts, Inc
    • Houston, Texas, United States, 77401
      • Research Concepts, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Scheduled for elective hip or knee replacement, reconstruction or arthroplasty surgery with anticipated need for post-operative intravenous (IV) morphine analgesia with anticipated use of (greater than or equal to (≥) 28 hours.
2. Adequate IV access
3. Anticipated hospital stay ≥ 28 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 80 years of age
4. Use of analgesics, muscle relaxants, NSAIDS and sedatives less than 12 hours prior to clinicaltrial material(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
5. Patients taking warfarin, lithium, combination of angiotension converting enzyme(ACE)-inhibitors and furosemide
6. Patients with anemia (active, clinically significant anemia) and/or a history or evidence of asthma or heart failure
7. History of allergy or hypersensitivity to any component of Caldolor, aspirin (or aspirin related products), NSAIDs, or COX-2 inhibitors
8. Pregnant or nursing
9. 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
10. Weigh less than 30 kilogram
11. Have a history of congenital bleeding diathesis (e.g. 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
12. Have gastrointestional (GI) bleeding that required medical intervention within the previous 6 weeks (unless definitive surgery has been performed)
13. Have a platelet count less than 30,000 mm^3 determined within the 28 days prior to surgery
14. Pre-existing dependence on narcotics or known tolerance to opioids
15. 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
16. Refusal to provide written authorization for use and disclosure of protected health information
17. Be on dialysis, have oliguria or creatinine greater than 3.0 milligram/deciliter.
18. Inability to achieve hemostasis or inability to close surgical incision, prior to Operating Room discharge
19. Operative procedure includes organ transplant
20. Pre or intra-operative procedure utilized for the prevention of pre- or post-operative pain (i.e. epidural or nerve blocks)
21. Be receiving full dose anticoagulation therapy or Activated Protein C within 6 hours before dosing (Prophylaxis with subcutaneous heparin is acceptable)
22. Have received another investigational drug within the past 30 days
23. 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; 250 milliliters normal saline as a placebo comparator was administered every 6 hours for a total of five doses over the first 24 hours. Those patients who received the initial five doses could continue to receive additional doses as needed every 6 hours through the 120-hour treatment period.	Other: Normal Saline; Placebo comparator; Other Names: NS
Experimental: Intravenous ibuprofen; 800 mg of intravenous ibuprofen diluted in 250 milliliters normal saline was administered every 6 hours for a total of five doses over the first 24 hours. Those patients who received the initial five doses could continue to receive additional doses as needed every 6 hours through the 120-hour treatment period.	Drug: Caldolor; 800 milligrams intravenous; Other Names: Ibuprofen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC-VAS With Movement (Post-operative Period, Hour-6-28)	Measurement of the patient's self assessment of pain with movement using the validated visual analog scale (VAS) during the post-operative period (study hour-6 through hour-28). VAS assessments document the patient's self reported level of pain from "No pain" (0 mm) to "Worst possible pain" (100 mm) on a 100 mm line. VAS assessments were performed immediately following surgery [variable since every surgery has a unique length of time even if it is the same procedure] and at hours 6, 8, 12, 16, 20, 24 and 28 (for the primary endpoint).	Study hour-6 through hour-28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Endpoint: AUC-VAS at Rest (Post-operative Period, Hours 6-28)	Measurement of the patient's self assessment of pain at rest using a visual analog scale (VAS) during the post-operative period (study hour-6 through hour-28). VAS assessments document the patient's self reported level of pain from "No pain" (0 mm) to "Worst possible pain" (100 mm) on a 100 mm line. VAS assessments were performed immediately following surgery and at hours 6, 8, 12, 16, 20, 24 and 28 (for the primary endpoint).	Study hour-6 through hour-28
Patient Demand of Narcotic Use (Post-operative Period, From Hour 6 to 28).	Patient demand of narcotic used by patients in each treatment group for analgesia, post-surgery.	Study hour-6 to hour-28

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Neil Singla, MD, Lotus Clinical Research/Methodist Hospital of Southern CA

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: May 7, 2007
• First Submitted That Met QC Criteria: May 7, 2007
• First Posted (Estimate): May 8, 2007

Study Record Updates

• Last Update Posted (Estimate): August 21, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: August 1, 2015

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-008C