Safety and Efficacy of Intravenous Acetaminophen (IV APAP... | NCT00598559

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1 g IV Acetaminophen	Experimental	1 g q6h IV Acetaminophen	Drug: IV Acetaminophen
650 mg IV Acetaminophen	Experimental	650 mg q4h IV Acetaminophen	Drug: IV Acetaminophen
Standard of Care	Other	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
IV Acetaminophen	Drug	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.

Outcomes Module

Primary Outcomes

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 Outcomes

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)

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Eugene Viscusi, MD	Thomas Jefferson University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Arcadia Methodist Hospital		Arcadia	California	91007	United States
Glendale Adventist Medical Center

ID	Title	Description
FG000	IV Acetaminophen 1 Gram Every 6 Hours	All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.
FG001	IV Acetaminophen 650 Milligram Every 4 Hours

ID	Title	Description
BG000	IV Acetaminophen 1g q6h	All Subjects Randomized to Receive IV acetaminophen 1g administered every 6 hours.
BG001	IV Acetaminophen 650 mg q4h	All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.
BG002	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.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00092 BG00191 BG00230 BG003213

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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)

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.

Posted

Sep 2009

Mean

Standard Deviation

Units on a scale

End of Day 5 (prior to discharge)

ID	Title	Description
OG000	IV Acetaminophen 1 g q6h	mITT Population, IV acetaminophen 1 g administered every 6 hours.
OG001	IV Acetaminophen 650 mg q4h	mITT Population, IV acetaminophen 650 mg administered every 4 hours.
OG002	Standard of Care (SOC)	mITT Population, Subjects Who Received Standard of Care Treatment.

Units	Counts
Participants	OG00064 OG00163 OG00226

Title

Denominators

Categories

Title	Measurements
	OG0002.5± 0.78 OG0012.5± 0.67 OG0022.0± 0.85

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).

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.

Posted

Sep 2009

Number

Participants

T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up

ID	Title	Description
OG000	IV Acetaminophen 1 g q6h	mITT Population, IV acetaminophen 1 g administered every 6 hours.
OG001	IV Acetaminophen 650 mg q4h	mITT Population, IV acetaminophen 650 mg administered every 4 hours.
OG002	Standard of Care (SOC)	mITT Population, Subjects Who Received Standard of Care Treatment.

Units

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

Posted

Number

Participants

First dose (T0) to within 30 days of the last dose of study medication.

ID	Title	Description
OG000	IV Acetaminophen 1 g q6h	mITT Population, IV acetaminophen 1 g administered every 6 hours.
OG001	IV Acetaminophen 650 mg q4h	mITT Population, IV acetaminophen 650 mg administered every 4 hours.
OG002	Standard of Care (SOC)	mITT Population, Subjects Who Received Standard of Care Treatment.

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.

Posted

Sep 2009

Mean

Standard Deviation

Units on a scale

Study period lookback at Day 7

ID	Title	Description
OG000	IV Acetaminophen 1 g q6h	mITT Population, IV acetaminophen 1 g administered every 6 hours.
OG001	IV Acetaminophen 650 mg q4h	mITT Population, IV acetaminophen 650 mg administered every 4 hours.
OG002	Standard of Care (SOC)	mITT Population, Subjects Who Received Standard of Care Treatment.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abscess	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Cardiac arrest	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0010 affected91 at risk EG0021 affected30 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Gastrointestinal anastomotic leak	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Haematoma	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Hepatic enzyme increased	Investigations	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0012 affected91 at risk EG0020 affected30 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Mental status changes	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Multi-organ failure	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Myocardial infarction	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Pelvic abscess	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Perirectal abscess	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Peritonitis	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Pneumonia	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Post procedural complication	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Postoperative ileus	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0021 affected30 at risk
Postoperative wound infection	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0002 affected92 at risk EG0012 affected91 at risk EG0020 affected30 at risk
Prostatic haemorrhage	Reproductive system and breast disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Renal failure acute	Renal and urinary disorders	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Sepsis	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0010 affected91 at risk EG0021 affected30 at risk
Staphylococcal infection	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk
Transaminases increased	Investigations	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Wound dehiscience	Injury, poisoning and procedural complications	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0020 affected30 at risk
Wound infection	Infections and infestations	MedDRA (10.0)	Non-systematic Assessment	EG0001 affected92 at risk EG0010 affected91 at risk EG0020 affected30 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG00011 affected92 at risk EG00110 affected91 at risk EG0026 affected30 at risk
Breath sounds abnormal	Investigations	MedDRA (10.0)	Non-systematic Assessment	EG0007 affected92 at risk EG0016 affected91 at risk EG0021 affected30 at risk
Constipation	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG00018 affected92 at risk EG00121 affected91 at risk EG0025 affected30 at risk
Headache	Nervous system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0007 affected92 at risk EG0015 affected91 at risk EG0024 affected30 at risk
Hypertension	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0006 affected92 at risk EG0015 affected91 at risk EG0020 affected30 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG00010 affected92 at risk EG0014 affected91 at risk EG0022 affected30 at risk
Hypotension	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0007 affected92 at risk EG0019 affected91 at risk EG0022 affected30 at risk
Insomnia	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG00013 affected92 at risk EG00117 affected91 at risk EG0025 affected30 at risk
Nausea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG00023 affected92 at risk EG00134 affected91 at risk EG0028 affected30 at risk
Oedema peripheral	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0007 affected92 at risk EG0017 affected91 at risk EG0022 affected30 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (10.0)	Non-systematic Assessment	EG00011 affected92 at risk EG00113 affected91 at risk EG0022 affected30 at risk
Vomiting	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0006 affected92 at risk EG00110 affected91 at risk EG0021 affected30 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (10.0)	Non-systematic Assessment	EG0003 affected92 at risk EG0010 affected91 at risk EG0022 affected30 at risk
Tachycardia	Cardiac disorders	MedDRA (10.0)	Non-systematic Assessment	EG0005 affected92 at risk EG0013 affected91 at risk EG0021 affected30 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (10.0)	Non-systematic Assessment	EG0005 affected92 at risk EG0014 affected91 at risk EG0021 affected30 at risk
Pyrexia	General disorders	MedDRA (10.0)	Non-systematic Assessment	EG0004 affected92 at risk EG0013 affected91 at risk EG0022 affected30 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0005 affected92 at risk EG0012 affected91 at risk EG0020 affected30 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (10.0)	Non-systematic Assessment	EG0005 affected92 at risk EG0012 affected91 at risk EG0022 affected30 at risk
Anxiety	Psychiatric disorders	MedDRA (10.0)	Non-systematic Assessment	EG0004 affected92 at risk EG0012 affected91 at risk EG0023 affected30 at risk
Phlebitis	Vascular disorders	MedDRA (10.0)	Non-systematic Assessment	EG0000 affected92 at risk EG0011 affected91 at risk EG0022 affected30 at risk

ID	Term
D059787	Acute Pain
D005334	Fever

ID	Term
D010146	Pain
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D001832	Body Temperature Changes

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	IV Acetaminophen 1 Gram Every 6 Hours	All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours.	14	92	60	92
EG001	IV Acetaminophen 650 Milligram Every 4 Hours	All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours.	11	91	68	91
EG002	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.	3	30	18	30