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

Phase 3

Completed

• Conditions: Pain
• Interventions: Other: Normal Saline; Drug: Caldolor

• Registration Number: NCT00470600
• Lead Sponsor: Cumberland Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05
• Study First Submitted: 2007-05-07
• Study First Submitted QC: 2007-05-07
• Study First Posted: 2007-05-08
• Primary Completion: 2008-09
• Study Completion: 2008-09
• Results First Submitted: 2011-04-07
• Results First Submitted QC: 2011-11-03
• Results First Posted: 2011-12-08
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-03
• Last Update Posted: 2015-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 185

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Saline	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.
Intravenous ibuprofen	Caldolor	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.

Primary Outcome Measures

Name	Time	Method
AUC-VAS With Movement (Post-operative Period, Hour-6-28)	Study hour-6 through hour-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).

Secondary Outcome Measures

Name	Time	Method
Secondary Endpoint: AUC-VAS at Rest (Post-operative Period, Hours 6-28)	Study hour-6 through hour-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).
Patient Demand of Narcotic Use (Post-operative Period, From Hour 6 to 28).	Study hour-6 to hour-28	Patient demand of narcotic used by patients in each treatment group for analgesia, post-surgery.

Trial Locations

Locations (9)

Research Concepts, Inc.; 🇺🇸 Houston, Texas, United States

Southeastern Center for Clinical Trials; 🇺🇸 Atlanta, Georgia, United States

Clinical Management Services, Inc.; 🇺🇸 Arcadia, California, United States

Eugene Marais Hospital; 🇿🇦 Pretoria, South Africa

Wilmax Clinical Research Inc.; 🇺🇸 Mobile, Alabama, United States

Teton Research, LLC; 🇺🇸 Little Rock, Arkansas, United States

Research Concepts, Inc; 🇺🇸 Houston, Texas, United States

Johannesburg General Hospital; 🇿🇦 Johannesburg, South Africa

Krugersdorp Private Hospital; 🇿🇦 Krugersdorp, South Africa