Acute Pain, Fever
Conditions
Keywords
Acute pain, Fever, IV Acetaminophen, Analgesic
Brief summary
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
• 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
Interventions
DRUGIV Acetaminophen
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.
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). | T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up | 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). |
| Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) | First dose (T0) to within 30 days of the last dose of study medication. | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments | End of Day 5 (prior to discharge) | 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) |
| Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. | Study period lookback at Day 7 | 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. |
Countries
United States
Participant flow
Recruitment details
Open label study conducted in the US from 21 Feb 2008 -12 Aug 2008
Participants by arm
| Arm | Count |
|---|---|
| IV Acetaminophen 1g q6h All Subjects Randomized to Receive IV acetaminophen 1g administered every 6 hours. | 92 |
| IV Acetaminophen 650 mg q4h All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours. | 91 |
| Standard of Care (SOC) All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them. | 30 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 7 | 0 |
| Overall Study | Early discharge from hospital | 9 | 12 | 3 |
| Overall Study | Protocol Non-compliance | 1 | 0 | 0 |
| Overall Study | Subject unable/unwilling to attend visit | 4 | 7 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | IV Acetaminophen 1g q6h | IV Acetaminophen 650 mg q4h | Standard of Care (SOC) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 44 Participants | 37 Participants | 13 Participants | 94 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 54 Participants | 17 Participants | 119 Participants |
| Sex: Female, Male Female | 49 Participants | 44 Participants | 17 Participants | 110 Participants |
| Sex: Female, Male Male | 43 Participants | 47 Participants | 13 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 92 | 68 / 91 | 18 / 30 |
| serious Total, serious adverse events | 14 / 92 | 11 / 91 | 3 / 30 |
Outcome results
Primary
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).
Time frame: T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up
Population: Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Acetaminophen 1 g q6h | Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). | 77 Participants |
| IV Acetaminophen 650 mg q4h | Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). | 86 Participants |
| Standard of Care (SOC) | Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE). | 26 Participants |
Primary
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
Time frame: First dose (T0) to within 30 days of the last dose of study medication.
Population: Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IV Acetaminophen 1 g q6h | Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) | 14 Participants |
| IV Acetaminophen 650 mg q4h | Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) | 11 Participants |
| Standard of Care (SOC) | Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE) | 3 Participants |
Secondary
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)
Time frame: End of Day 5 (prior to discharge)
Population: Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen 1 g q6h | Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments | 2.5 Units on a scale | Standard Deviation 0.78 |
| IV Acetaminophen 650 mg q4h | Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments | 2.5 Units on a scale | Standard Deviation 0.67 |
| Standard of Care (SOC) | Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments | 2.0 Units on a scale | Standard Deviation 0.85 |
Secondary
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.
Time frame: Study period lookback at Day 7
Population: Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen 1 g q6h | Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. | 2.4 Units on a scale | Standard Deviation 0.75 |
| IV Acetaminophen 650 mg q4h | Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. | 2.3 Units on a scale | Standard Deviation 0.74 |
| Standard of Care (SOC) | Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period. | 2.2 Units on a scale | Standard Deviation 0.61 |