A Phase 4 interventional study of acetaminophen and placebo in Drug Toxicity and Healthy, sponsored by Denver Health and Hospital Authority. Completed at 2 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2013-09-18.
Sponsored by Denver Health and Hospital Authority · Phase 4 and Interventional
The objective of this study is to monitor liver function tests (blood levels of an indicator of liver function) of healthy people taking the maximum labeled daily dose of acetaminophen compared to people taking placebo for 16 to 40 days. Those people that continue to have normal liver tests after 16 days will have completed their part of the study. People that develop abnormal liver function tests will continue taking acetaminophen or placebo, and have their liver tests monitored closely for up to an additional 24 days. This is to (1) make sure these tests return to normal and (2) determine when these tests return to normal while still taking acetaminophen or placebo. If at any time the liver tests indicate anything more than a minor increase, you would be immediately told to stop taking the study drug.
Secondary objective is to determine the proportion of subjects that have detectable acetaminophen-protein adducts after daily dosing.
Acetaminophen use is common and many consumers take 4g/day for longer than 4 days. The use of 4g/day of acetaminophen for more than 4 days causes an asymptomatic ALT elevation in some people. This elevation most likely resolves while continuing treatment, but it is possible that some individuals may go on to develop clinical liver injury. By carefully following healthy subjects who are taking the maximal daily dose of acetaminophen, we can safely determine if the ALT elevation resolves or progresses to clinical liver injury. If a subject develops clinical liver injury we can intervene before irreversible injury occurs.
437 studies on the registry are indexed under Drug-Related Side Effects and Adverse Reactions; 76 are open to participants now.
This study's enrollment of 398 is above the median of 103 across 255 interventional studies indexed under Drug-Related Side Effects and Adverse Reactions.
Browse Drug-Related Side Effects and Adverse Reactions studies →Denver Health and Hospital Authority is the lead sponsor of 84 studies on the registry; 4 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.
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Exclusion Criteria:
acetaminophen, 4 grams/day (1 gram every 4 hours for 4 doses)
Drug: acetaminophen
placebo for acetaminophen 4 grams/day (2 caplets every 4 hours for 4 doses)
Drug: placebo
500 mg caplets; 2 caplets (1 g)/dose; 4 doses (4 g)/day, 4 hours apart for 16 to 40 days.
Also known as: tylenol
placebo caplets, 2 caplets per dose, 4 doses per day, 4 hours apart for 16 to 40 days
The Proportion of Subjects Treated With Long-term Acetaminophen (4 g/Day) That Develops Persistent ALT Elevations.
ALT was measured on Day 0 and 16 for all study participants. Subjects with an elevated ALT at Day 16 continued dosing with study drug and continued to have their ALT measured every three days until the ALT elevation resolved or until Day 40. Persistent ALT elevation was defined as any subject with an unresolved ALT elevation at study Day 40.
Time frame: serial samples for 16-40 days
The Proportion of Subjects With Detectable Serum Acetaminophen-cysteine Adduct (APAP-cys) Concentrations 1, 2, and 3 Days After Starting the Maximal Recommended Dosing of Acetaminophen (4 g/Day).
Time frame: Days 1-3
Recruitment took place from August 2008 through August 2011 in the Denver Metro area. Healthy volunteers were recruited from the community through the use of approved advertisements.
| Milestone | Acetaminophen Arm | Placebo Arm |
|---|---|---|
| Started | 224 | 52 |
| Completed | 205 | 47 |
| Not completed | 19 | 5 |
| Milestone | Acetaminophen Arm | Placebo Arm |
|---|---|---|
| Started | 51 | 1 |
| Completed | 48 | 1 |
| Not completed | 3 | 0 |
ALT was measured on Day 0 and 16 for all study participants. Subjects with an elevated ALT at Day 16 continued dosing with study drug and continued to have their ALT measured every three days until the ALT elevation resolved or until Day 40. Persistent ALT elevation was defined as any subject with an unresolved ALT elevation at study Day 40.
| participants | Acetaminophen Arm | Placebo Arm |
|---|---|---|
| Subjects without persisitent ALT elevation | 204 | 47 |
| Subjects with persistent ALT elevation | 1 | 0 |
| participants | Acetaminophen Arm | Placebo Arm |
|---|---|---|
| Day 1-No. Subjects with Detectable APAP-cys | 7 | 1 |
| Day 2-No. Subjects with Detectable APAP-cys | 57 | 1 |
| Day 3-No. Subjects with Detectable APAP-cys | 59 | 1 |
Collected over Adverse events were collected starting at the time of consent through study completion.. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Acetaminophen Arm | — | 0/224 (0%) | 147/224 (65.6%) |
| Placebo Arm | — | 0/52 (0%) | 25/52 (48.1%) |
| Event | Acetaminophen Arm | Placebo Arm |
|---|---|---|
| Gastrointestinal DisordersGastrointestinal disorders | 70/224 | 10/52 |
| Nervous system disordersNervous system disorders | 42/224 | 11/52 |
| Muskuloskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders | 26/224 | 5/52 |
| General disorders and administration site conditionsGeneral disorders | 23/224 | 3/52 |
| Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 23/224 | 5/52 |
| Infections and infestationsInfections and infestations | 14/224 | 2/52 |
| Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications | 10/224 | 2/52 |
| Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders | 9/224 | 0/52 |
| Vascular disordersVascular disorders | 9/224 | 1/52 |
| Psychiatric disordersPsychiatric disorders | 6/224 | 1/52 |
Baseline characteristics were collected on all subjects at screening and included: race, ethnicity, gender, age, weight, and height. The number of participants included in the analysis (276) is based on the safety population, which includes any subject that took at least one dose of study medication.
| Age, Categorical(Participants) | Acetaminophen Arm | Placebo Arm | Total |
|---|---|---|---|
| <=18 years | 1 | 0 | 1 |
| Between 18 and 65 years | 221 | 52 | 273 |
| >=65 years | 2 | 0 | 2 |
| Age Continuous(years) | Acetaminophen Arm | Placebo Arm | Total |
|---|---|---|---|
| Mean | 36.3 ± 12.16 | 35.8 ± 12.50 | 36.2 ± 12.21 |
| Sex: Female, Male(Participants) | Acetaminophen Arm | Placebo Arm | Total |
|---|---|---|---|
| Female | 163 | 39 | 202 |
| Male | 61 | 13 | 74 |
| Region of Enrollment(participants) | Acetaminophen Arm | Placebo Arm | Total |
|---|---|---|---|
| United States | 224 | 52 | 276 |
This study is completed, as verified in Sep 2013. You cannot join it, but the record below documents what was studied.
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Drug-Related Side Effects and Adverse Reactions→
Denver Health and Hospital Authority