Pain
Conditions
Brief summary
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
Interventions
OTHERNormal 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)
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)
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Patient Demand for the Narcotic Analgesic, Morphine, Post Surgery | 24 Hours | Change in the amount of morphine use (in milligrams) by subjects in each treatment group for a 24 hour period post-surgery |
Countries
Australia, United States
Participant flow
Recruitment details
Participants were recruited from the medical practices and/or clinics of the investigator/sub-investigators.
Pre-assignment details
A total of 319 participants were randomized into two treatment groups. Randomized participants were additionally stratified by age and weight; three participants were randomized to incorrect stratification categories. All 319 participants received at least one dose of clinical trial material.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The first dose of intravenous placebo will be administered at approximately the initiation of skin closure, prior to discharge to the recovery room. Seven subsequent doses of intravenous placebo will be administered every 6 hours. After receiving 8 doses of intravenous placebo, intravenous placebo will continue to be administered every 6 hours up to 5 days post surgery if pain medication is still required and intravenous access is present. All participants were able to receive morphine until approximately 45 minutes before the end of surgery. At that time on only fentanyl will be allow until the end of the surgery. Upon discharge from the operating room, participants will have access to morphine upon patient request or delivered by patient controlled analgesia. | 153 |
| 800 mg Intravenous Ibuprofen The first dose of intravenous ibuprofen will be administered at approximately the initiation of skin closure, prior to discharge to the recovery room. Seven subsequent doses of intravenous ibuprofen will be administered every 6 hours. After receiving 8 doses of intravenous ibuprofen, intravenous ibuprofen will continue to be administered every 6 hours up to 5 days post surgery if pain medication is still required and intravenous access is present. All participants were able to receive morphine until approximately 45 minutes before the end of surgery. At that time on only fentanyl will be allow until the end of the surgery. Upon discharge from the operating room, participants will have access to morphine upon patient request or delivered by patient controlled analgesia. | 166 |
| Total | 319 |
Baseline characteristics
| Characteristic | Placebo | 800 mg Intravenous Ibuprofen | Total |
|---|---|---|---|
| Age, Customized 45 to 70 years of age | 49 participants | 56 participants | 105 participants |
| Age, Customized Less than or equal to 45 years | 104 participants | 110 participants | 214 participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 91 Participants | 84 Participants | 175 Participants |
| Race/Ethnicity, Customized Caucasian | 52 Participants | 71 Participants | 123 Participants |
| Race/Ethnicity, Customized Hispanic | 8 Participants | 11 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 153 participants | 166 participants | 319 participants |
| Sex: Female, Male Female | 153 Participants | 166 Participants | 319 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight Greater than 75 kilograms | 96 Kilograms | 105 Kilograms | 201 Kilograms |
| Weight Less than or equal to 75 kilograms | 57 Kilograms | 61 Kilograms | 118 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 149 / 153 | 150 / 166 |
| serious Total, serious adverse events | 6 / 153 | 12 / 166 |
Outcome results
Primary
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
Time frame: 24 Hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in the Patient Demand for the Narcotic Analgesic, Morphine, Post Surgery | 57.0 milligrams | Standard Error 2.4 |
| 800 mg Intravenous Ibuprofen | Change in the Patient Demand for the Narcotic Analgesic, Morphine, Post Surgery | 48.7 milligrams | Standard Error 2.3 |