A Phase 1/2 interventional study of Bromocriptine 5 MG and Acetaminophen 650 MG in Subarachnoid Hemorrhage, Subdural Hematoma and Traumatic Brain Injury, sponsored by University of California, San Francisco. Completed at 2 sites in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2021-06-24.
Sponsored by University of California, San Francisco · Phase 1/2, Interventional, and Treatment
The purpose of this study is to evaluate the antipyretic effect of bromocriptine in critically-ill patients with acute neurologic injury and fever from infectious and non-infectious etiologies.
In patients with acute neurologic injury such as subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic brain injury (TBI), subdural hematoma (SDH), and ischemic stroke, fever has been found to be an independent predictor of poor outcome including increased mortality rates, longer hospital stays, depressed level of consciousness, and worse functional outcomes. Our current antipyretic therapy of acetaminophen and sometimes nonsteroidal anti-inflammatory drugs are not very effective and external cooling requires sedatives and other medications to prevent shivering and pain. Bromocriptine is a dopamine D2 receptor agonist which acts at the hypothalamus, a specific area of the brain that regulates body temperature. Fevers of both central and infectious etiologies must be regulated through the hypothalamus and we have evidence that bromocriptine has an antipyretic effect at the hypothalamus; thus, we hypothesize that bromocriptine could be used safely and more broadly to treat all fevers in the acute setting and not just refractory central fevers in this patient population.
Here, we propose to evaluate the acute antipyretic effects of bromocriptine in this critically-ill population through a pilot, open label, blinded endpoint, randomized controlled trial. In both enrolling centers, University of California, San Francisco Medical Center Parnassus (UCSF) and Zuckerberg San Francisco General Hospital, every patient who is admitted to the neurointensive care unit for an anticipated stay of greater than 48 hours with a diagnosis of subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic brain injury (TBI), subdural hematoma (SDH), and ischemic stroke will be screened and consented. If they have a temperature reading ≥ 38.3 ºC, the investigational pharmacy will randomize them to the control arm of acetaminophen or the intervention arm of acetaminophen and bromocriptine for 48 hours. We will continuously measure their temperature and other vitals data. Retrospectively, we will review imaging and labs ordered to work up infectious etiologies of fever. The ICU nurse will do a 5 minute assessment every shift during the 48 hour study period for side effects. The temperature data will be analyzed between the two study arms.
510 studies on the registry are indexed under Subarachnoid Hemorrhage; 128 are open to participants now.
This study's enrollment of 47 is below the median of 57 across 264 interventional studies indexed under Subarachnoid Hemorrhage.
Browse Subarachnoid Hemorrhage studies →University of California, San Francisco is the lead sponsor of 2,169 studies on the registry; 372 are open to participants now.
Of its 267 completed or terminated interventional studies of FDA-regulated products, 202 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Standard of care - acetaminophen 650mg every 4 hours PO/NG/FT (per oral, nasogastric tube, feeding tube) for 48 hours, initiated within 1 hour after temperature reading ≥ 38.3ºC.
Drug: Acetaminophen 650 MG
Bromocriptine 5mg every 4 hours PO/NG/FT for 48 hours and acetaminophen 650mg every 4 hours PO/NG/FT for 48 hours, initiated within 1 hour after temperature reading ≥ 38.3ºC.
Drug: Bromocriptine 5 MG · Drug: Acetaminophen 650 MG
Bromocriptine 5 mg every 4 hours PO/NG/FT
Also known as: parlodel
Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours
Also known as: Tylenol
Temperature Burden
Mean total body temperature burden above 37°C over 48 hours during which patient receives either control or intervention medication.
Time frame: over 48 hours
Incidence of Adverse Events - Symptomatic Hypotension, Nausea and Headache
Episodes of symptomatic hypotension, including decrease in supine systolic and diastolic pressures of greater than 20mm and 10mm Hg respectively with patient reported accompanying symptoms of light headedness or dizziness and incidence of nausea and headache.
Time frame: Nursing assessment at every shift during 48 hour study period after first drug administration
Total Time That Temperature is ≥ 38.3ºC
Time in minutes where the temperature is ≥ 38.3ºC during the 48 hours of control versus intervention administration.
Time frame: 48 hours
Total Time to First Temperature < 37.5ºC
Time in minutes it took after medication administration for the temperature to reach \< 37.5ºC.
Time frame: 48 hours
| Milestone | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Started | 21 | 26 |
| Completed | 20 | 24 |
| Not completed | 1 | 2 |
Mean total body temperature burden above 37°C over 48 hours during which patient receives either control or intervention medication.
| Temperature in degrees Celsius | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Temperature Burden | 37.8 ± 0.5 | 37.7 ± 0.6 |
Episodes of symptomatic hypotension, including decrease in supine systolic and diastolic pressures of greater than 20mm and 10mm Hg respectively with patient reported accompanying symptoms of light headedness or dizziness and incidence of nausea and headache.
| Participants | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Decrease in blood pressure | 12 | 17 |
| Nausea | 2 | 3 |
| Headache | 8 | 12 |
Time in minutes where the temperature is ≥ 38.3ºC during the 48 hours of control versus intervention administration.
| Minutes | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Total Time That Temperature is ≥ 38.3ºC | 216 (85.5 to 1118) | 300 (85.5 to 739) |
Time in minutes it took after medication administration for the temperature to reach \< 37.5ºC.
| Minutes | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Total Time to First Temperature < 37.5ºC | 253.5 (170.5 to 722.5) | 556 (286.5 to 772.5) |
Collected over 48 hours. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Acetaminophen | 0/21 (0%) | 0/21 (0%) | 17/21 (81%) |
| Bromocriptine and Acetaminophen | 1/26 (3.8%) | 1/26 (3.8%) | 23/26 (88.5%) |
| Event | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| HospitalizationGeneral disorders | 0/21 | 1/26 |
| Event | Acetaminophen | Bromocriptine and Acetaminophen |
|---|---|---|
| Blood pressure decreaseCardiac disorders | 12/21 | 17/26 |
| HeadacheGeneral disorders | 8/21 | 12/26 |
| Hypotension required treatmentCardiac disorders | 5/21 | 9/26 |
| OrthostasisCardiac disorders | 4/21 | 5/26 |
| NauseaGeneral disorders | 2/21 | 3/26 |
| Age, Continuous(years) | Acetaminophen | Bromocriptine and Acetaminophen | Total |
|---|---|---|---|
| Median | 56.5 (44.5 to 69) | 60.5 (44 to 69) | 59.5 (44 to 69) |
| Sex: Female, Male(Participants) | Acetaminophen | Bromocriptine and Acetaminophen | Total |
|---|---|---|---|
| Female | 10 | 8 | 18 |
| Male | 10 | 16 | 26 |
| Race/Ethnicity, Customized(Participants) | Acetaminophen | Bromocriptine and Acetaminophen | Total |
|---|---|---|---|
| Caucasian | 9 | 6 | 15 |
| Black | 0 | 1 | 1 |
| Hispanic | 6 | 9 | 15 |
| Asian/Pacific Islander | 4 | 8 | 12 |
| Other | 1 | 0 | 1 |
| Region of Enrollment(Participants) | Acetaminophen | Bromocriptine and Acetaminophen | Total |
|---|---|---|---|
| United States | 20 | 24 | 44 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — There is no plan to make IPD available to other researchers as this data is very specific to this study.
Ran from Nov 2018 to primary completion in Nov 2019, 11 months.
Results were first posted in Jun 2021, 1 year 7 months after primary completion.
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Studies of the drug tested here: Bromocriptine
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