A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Ibuprofen 400 and 800 mg Every 6 Hours in the Management of Postoperative Pain.

Study Overview
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Brief Summary
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This study was to evaluate the efficacy and safety of intravenously administered ibuprofen 400mg and 800 mg q6h for the management of moderate to severe postoperative pain in Chinese population.

Detailed Description
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This randomized, parallel, double-blind, placebo controlled multi-center clinical study was conducted in 396 patients scheduled to undergo elective general anesthesia laparotomy or orthopedic surgery. Patients were randomly divided into three groups in radio 1:1:1 received respectively IV placebo, ibuprofen 400 mg or ibuprofen 800 mg. The first dose of study drugs was administered intravenously at the time of wound closure and then every 6 hours within 48 hours after the operation. At the end of surgical suture, 5mg morphine was injected intravenously, and then the patient-controlled intravenous analgesia pump was connected. Efficacy was assessed by morphine dosage during the first 24 hours, pain intensity score, and area under the pain-time curve after surgery. Safety was assessed by the incidence of adverse events.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Ibuprofen 400 and 800 mg Every 6 Hours in the Management of Postoperative Pain.

Conditions
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Intravenous, Ibuprofen, Nonsteroidal Anti-inflammatory Drug, Injectable, Pain, Analgesic

Intervention / Treatment
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* Drug: ibuprofen
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Enrollment was open to patients undergoing scheduled abdominal surgery (intestinal or lower abdomen) or orthopedic surgery (such as knee arthroplasty or shoulder joint reconstruction) under general anesthesia with endotracheal intubation and were expected to require patient-controlled intravenous analgesia (PCIA) pump for more than 24h for moderate to severe pain after surgery. Exclusion Criteria: Those who can not understand the NRS score and cooperate with the evaluation; those who had head trauma or complicated with organic lesions of the central nervous system within 4 weeks before operation; those who developed coagulation dysfunction or took anticoagulants and antiplatelet drugs; those with a history of severe cardio-cerebrovascular disease, heart failure; those with liver and kidney dysfunction, severe endocrine system diseases, mental illness; those with a history of peptic ulcer or bleeding; those who did not control grade 2 or above hypertension or were still taking two or more of antihypertensive drugs such as angiotensin converting enzyme inhibitors (ACEI), angiotensin converting enzyme antagonists (ARB) and diuretics at admission; Increased toxicity due to the interaction of methotrexate, lithium preparations, etc. with the test drug; use of NSAIDs or analgesic muscle relaxants within 24 hours before operation, narcotic dependence or tolerance; allergy to ibuprofen or other NSAIDs; pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ibuprofen( 400mg group)<br>Patients were randomly divided into the group received respectively IV ibuprofen 400 mg . | Drug: ibuprofen<br>* Patients were randomly divided into three groups in radio 1:1:1 received respectively IV placebo, ibuprofen 400 mg or ibuprofen 800 mg. The first dose of study drugs was administered intravenously at the time of wound closure and then every 6 hours within 48 hours after the operation.<br>|
| Experimental: ibuprofen( 800mg group)<br>Patients were randomly divided into the group received respectively IV ibuprofen 800 mg. | Drug: ibuprofen<br>* Patients were randomly divided into three groups in radio 1:1:1 received respectively IV placebo, ibuprofen 400 mg or ibuprofen 800 mg. The first dose of study drugs was administered intravenously at the time of wound closure and then every 6 hours within 48 hours after the operation.<br>|
| Placebo Comparator: placebo group<br>Patients were randomly divided into the group received respectively IV placebo,. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the amount of morphine administered | after surgery. | during the first 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity (PI) | the PI was evaluated using patient self-reporting with numerical rating scales (NRS) (0= no pain to 10= intense pain) | at 0 hour,1 hour, 2 hours, 3 hours, 6 hours, 12 hours, 18 hours, 24 hours, 30 hours, 36 hours, 42 hours and 48 hours immediately after the first administration. | 
| The area under the PI-time curve (AUC) | at rest and with movement | across 3 time periods (1-24 hours, 6-24 hours, 12-24 hours) | 
| Total frequency and effective frequency of PCA | after surgery | within 24 hours | 
| Treatment failure rate | the rate of using other non-morphine drugs to remedy analgesia | within 24 hours after the operation | 
| Patients' evaluation of the study drug | excellent=5, very good=4, good=3, general=2, bad=1 | after 48 hours of medication |