Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients

Study Overview
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Brief Summary
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The study will be investigating safety and efficacy administration of repeated dose of IV Acetaminophen (IV APAP) over five days for the treatment of acute pain or fever in adult patients.

Detailed Description
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• To assess the safety of IV Acetaminophen when used over five days for the treatment of acute pain or fever in adult inpatients Secondary Objectives: To compare the efficacy of IV Acetaminophen 650 milligram (mg) every four (q4) hours vs. 1 gram (g) every 6 (q6) hours over 5 days of treatment To compare the safety of IV Acetaminophen 650 mg q4 hours vs. 1 g q6 hours over 5 days of treatment To compare the safety of IV Acetaminophen vs. standard of care (SOC) treatment over 5 days of treatment To compare the efficacy of IV Acetaminophen vs. standard of care treatment over 5 days of treatment

Official Title
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A Phase III, Multi-Center, Open-Label, Prospective, Repeated Dose, Randomized, Controlled, Multi-Day Study of the Safety and Efficacy of Intravenous Acetaminophen in Adult Inpatients

Conditions
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Acute Pain, Fever

Intervention / Treatment
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* Drug: IV Acetaminophen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent prior to participation in the Study Be at least 18 years of age and weigh at least 41 kilogram (kg) Be anticipated by the Investigator to require multi-day (target is five days) use of IV treatment either because of having a nothing by mouth (NPO) status having a medical condition that makes oral intake difficult having a medical condition that requires IV treatment Be willing to undergo 5 days of treatment with IV acetaminophen for the treatment of pain or fever (defined as a core temperature greater than or equal to 38 degrees celsius). Note that Subjects have a slightly less than 15% chance (one in seven) of being assigned to the Control Group and receiving standard of care treatment, but no IV APAP. Have the ability to read and understand the Study procedures and have the ability to communicate meaningfully with the Study Investigator and staff If a female of child bearing potential, have a negative pregnancy test within 48 hours of randomization Exclusion Criteria: Has a significant medical disease, laboratory abnormality or condition that, in the Investigator's judgment, could compromise the Subject's welfare or would otherwise contraindicate Study participation Is expected to have difficulty in communicating with the Study staff or completing Study requirements (including follow up visits) Has known hypersensitivity to acetaminophen or the inactive ingredients (excipients) of IV acetaminophen or any contraindication to receiving acetaminophen Has impaired liver function, e.g., Alanine aminotransferase (ALT) greater than or equal to 3 times the upper limit of normal (ULN), bilirubin greater than or equal to 3 times ULN, known active hepatic disease (e.g., hepatitis), evidence of clinically significant chronic liver disease or other condition affecting the liver (e.g., alcoholism as defined by DSM-IV, cirrhosis or chronic hepatitis) Has participated in an interventional clinical Study (investigational or marketed product) within 30 days of Study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 g IV Acetaminophen<br>1 g q6h IV Acetaminophen | Drug: IV Acetaminophen<br>* Arm 1: 1 g IV Acetaminophen every 6 hours administered for five days. Arm 2: 650 mg IV Acetaminophen every 4 hours administered for five days. Arm 3: The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen.<br>* Other names: IV Acetaminophen (IV APAP);|
| Experimental: 650 mg IV Acetaminophen<br>650 mg q4h IV Acetaminophen | Drug: IV Acetaminophen<br>* Arm 1: 1 g IV Acetaminophen every 6 hours administered for five days. Arm 2: 650 mg IV Acetaminophen every 4 hours administered for five days. Arm 3: The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen.<br>* Other names: IV Acetaminophen (IV APAP);|
| Other: Standard of Care<br>The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen. | Drug: IV Acetaminophen<br>* Arm 1: 1 g IV Acetaminophen every 6 hours administered for five days. Arm 2: 650 mg IV Acetaminophen every 4 hours administered for five days. Arm 3: The standard of care treatments were defined as any medication the investigator deemed appropriate to treat the subject, including products containing acetaminophen but excluding IV acetaminophen.<br>* Other names: IV Acetaminophen (IV APAP);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). | Number of subjects who experienced at least one treatment emergent adverse event (TEAE). A TEAE is an adverse event that occurs on or after the first dose of study medication (T0). | T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up | 
| Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) | Serious TEAE is any untoward medical occurrences at any dose of study medication that: results in death is life threatening requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity is a congenital anomaly/birth defect is an important medical event | First dose (T0) to within 30 days of the last dose of study medication. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments | Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with side effects related to study treatment at End of Day 5 (prior to discharge) | End of Day 5 (prior to discharge) | 
| Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. | Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with study treatments looking back over the entire treatment period was conducted at Day 7. | Study period lookback at Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute pain, Fever, IV Acetaminophen, Analgesic