Pain
Conditions
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.
Interventions
DRUGCaldolor
800 milligrams intravenous
OTHERNormal Saline
Placebo comparator
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 250 mL of normal saline. | 86 |
| 800mg IV Ibuprofen (Caldolor) 8 mL of IV Ibuprofen (Caldolor) added with 250 mL of normal saline to give 800 mg dose. | 99 |
| Total | 185 |
Baseline characteristics
| Characteristic | Placebo | 800mg IV Ibuprofen (Caldolor) | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 9.9 | 62 years STANDARD_DEVIATION 10.3 | 61 years STANDARD_DEVIATION 10.2 |
| Age, Customized <45years | 6 participants | 3 participants | 9 participants |
| Age, Customized >= 45 years | 80 participants | 96 participants | 176 participants |
| Region of Enrollment South Africa | 25 participants | 29 participants | 54 participants |
| Region of Enrollment United States | 61 participants | 70 participants | 131 participants |
| Sex: Female, Male Female | 55 Participants | 65 Participants | 120 Participants |
| Sex: Female, Male Male | 31 Participants | 34 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 74 / 86 | 90 / 99 |
| serious Total, serious adverse events | 3 / 86 | 8 / 99 |
Outcome results
Primary
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).
Time frame: Study hour-6 through hour-28
Population: Efficacy analyses were performed on the Intent to Treat (ITT) population and the Efficacy Evaluable Population (EEP). All randomized patients who received at least a partial dose of CTM were included in the ITT analyses. All data below represents the ITT analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC-VAS With Movement (Post-operative Period, Hour-6-28) | 1326.1 AUC-VAS pain v. time (mm*hr) | Standard Error 82 |
| 800mg IV Ibuprofen (Caldolor) | AUC-VAS With Movement (Post-operative Period, Hour-6-28) | 1005.0 AUC-VAS pain v. time (mm*hr) | Standard Error 81.5 |
Secondary
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.
Time frame: Study hour-6 to hour-28
Population: Demand of narcotic use was determined by PCA records or by chart if patient requested and not via PCA.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Patient Demand of Narcotic Use (Post-operative Period, From Hour 6 to 28). | 59.5 milligrams | Standard Deviation 29.9 |
| 800mg IV Ibuprofen (Caldolor) | Patient Demand of Narcotic Use (Post-operative Period, From Hour 6 to 28). | 41.1 milligrams | Standard Deviation 27.3 |
Secondary
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).
Time frame: Study hour-6 through hour-28
Population: Efficacy analyses were performed on the Intent to Treat (ITT) population and the Efficacy Evaluable Population (EEP). All randomized patients who received at least a partial dose of CTM were included in the ITT analyses. All data below represents the ITT analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Secondary Endpoint: AUC-VAS at Rest (Post-operative Period, Hours 6-28) | 997.0 AUC-VAS pain v. time (mm*hr) | Standard Error 83.6 |
| 800mg IV Ibuprofen (Caldolor) | Secondary Endpoint: AUC-VAS at Rest (Post-operative Period, Hours 6-28) | 728.0 AUC-VAS pain v. time (mm*hr) | Standard Error 83 |