FeverPhase 4NCT01530880
Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
A Phase 4 study testing Intravenous Ibuprofen in people with Fever, run by Columbia University at 1 site in United States.
Trial summary
Fever, defined as temperature higher than 38.3C (100.9 F), is common in patients with head injuries and is associated with poor recovery after injury. The current standard of care is to use oral acetaminophen (Tylenol) followed by a body cooling device. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fever
- What is being tested?
- Intravenous Ibuprofen
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to 17 Mar 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after admission.
- Intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) < 10
- Presence of intraventricular hemorrhage on initial brain computerized tomography (CT) scan
Who cannot join
- Imminent death within 72 hours of admission.
- Plan for discharge from the Neuro intensive care unit (ICU) within 72 hours of admission.
- Diagnosis with sepsis (Systemic inflammatory response syndrome (SIRS) criteria plus the presence of known or suspected infection)
- Presence of coagulopathy (international normalized ratio (INR) > 1.7)
- Thrombocytopenia (platelet count < 100,000)
- History of gastrointestinal bleed
Show all 11Show fewer
- Abnormal liver function tests (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/alkaline phosphatase (AP)/Gamma-glutamyl transferase (GGT) 2x normal)
- Hypersensitivity to ibuprofen
- Pregnancy as determined by urine beta human chorionic gonadotropin (hCG), or lactating postpartum women
- Renal impairment (Creatinine > 1.5 mg/dL)
- Measured body weight < 50 kg
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Fever, defined as temperature higher than 38.3C (100.9 F), is common in patients with head injuries and is associated with poor recovery after injury. The current standard of care is to use oral acetaminophen (Tylenol) followed by a body cooling device. This method can effectively reduce fever but results in a high rate of shivering. Shivering is stressful to the heart and can further worsen brain injury. Methods to combat shivering have been developed and are successful in limiting the stress in the majority of patients that use a body cooling device. However, the drugs used to control shivering are sedating and may also interfere with brain recovery.
The purpose of this study is to assess whether ibuprofen given intravenously is more effective in combating fever than the current standard of care. Should results from this study demonstrate that ibuprofen infusion is effective, a larger study will be conducted to determine whether this aggressive fever control regimen leads to improved recovery after brain injury.
Read the detailed description
This is an open-label, investigator initiated single center, randomized, prospective study. Subjects meeting enrollment criteria will be randomly assigned 1:1 to one of two groups:
- Standard Care: Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
- Ibuprofen 400 mg/100 mL NS IV over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL NS at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
Patients/surrogates will be approached for consent and randomized upon admission. Therapy will only be initiated once a patient becomes febrile (>=38.3 C, 100.9 F). The use of temperature modulating devices will be permitted as per institutionally approved guidelines in those patients continuing to demonstrate a fever (T>38.3 C, 100.9 F) with either therapy.
- Conditions
- Fever
- Being tested
- Intravenous Ibuprofen, Acetaminophen (Standard of Care)
- Keywords
- Fever reduction, Fever burden, intravenous ibuprofen
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous IbuprofenDrug
Also called Caldolor
Ibuprofen 400 mg/100 mL intravenous (IV) over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first
Acetaminophen (Standard of Care)Drug
Also called Tylenol
Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Ibuprofen | Experimental | Patients assigned to the ibuprofen treatment group will receive a 400 mg IV ibuprofen bolus over 30 minutes followed by an infusion of ibuprofen at 85 mg/hr. Receives: Drug: Intravenous Ibuprofen |
| Standard of Care | Other | Patients assigned to the standard of care group will be given 650 mg of oral acetaminophen and continue to receive 650 mg of oral acetaminophen every 6 hours as needed to maintain temperature < 38.3 C (100.9 F). Receives: Drug: Acetaminophen (Standard of Care) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of Fever Burden
Reduction in fever burden (degrees C x hours) with intravenous ibuprofen infusion as compared to oral acetaminophen over duration of treatment. Fever burden is calculated hourly by subtracting each patient's recorded temperature (from either a bladder or esophageal temperature probe) from 37 degrees C.
Measured: Up to14 days
Secondary outcomes (3)
Mean Difference in Inflammatory Markers
Mean difference in markers of inflammation between IV ibuprofen and standard of care groups
Measured: Up to 14 days
Difference in Cost Between Ibuprofen and Acetaminophen
Cost analysis of aggressive fever control (AFC) between patients randomized to either intravenous ibuprofen infusion or standard of care (oral acetaminophen).
Measured: Up to 14 days
Bleeding Incidence
Incidence of bleeding (defined by a priori criteria)
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2012 (estimated)
- Study startOct 2012
- Primary completion17 Mar 2016
- Study completion17 Mar 2016
Why it stopped: PI no longer at institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Cumberland Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- J. Michael Schmidt, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01530880
- Sponsor's protocol ID
- AAAI1788
- Status last verified
- Aug 2017
- First submitted
- 8 Feb 2012
- Last updated
- 28 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aggressive Fever Control With Intravenous Ibuprofen After Non-traumatic Brain Hemorrhage
- ClinicalTrials.gov ID
- NCT01530880
- Acronym / sponsor ID
- AAAI1788
- Conditions
- Fever
- Keywords
- Fever reduction, Fever burden, intravenous ibuprofen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI no longer at institution
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Cumberland Pharmaceuticals
- Study start
- Oct 2012
- Primary completion
- 17 Mar 2016 (actual)
- Study completion
- 17 Mar 2016 (actual)
- First posted
- 10 Feb 2012 (estimated)
- Results
- Posted 28 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fever, defined as temperature higher than 38.3C (100.9 F), is common in patients with head injuries and is associated with poor recovery after injury. The current standard of care is to use oral acetaminophen (Tylenol) followed by a body cooling device. This method can effectively reduce fever but results in a high rate of shivering. Shivering is stressful to the heart and can further worsen brain injury. Methods to combat shivering have been developed and are successful in limiting the stress in the majority of patients that use a body cooling device. However, the drugs used to control shivering are sedating and may also interfere with brain recovery.
The purpose of this study is to assess whether ibuprofen given intravenously is more effective in combating fever than the current standard of care. Should results from this study demonstrate that ibuprofen infusion is effective, a larger study will be conducted to determine whether this aggressive fever control regimen leads to improved recovery after brain injury.
Detailed description
This is an open-label, investigator initiated single center, randomized, prospective study. Subjects meeting enrollment criteria will be randomly assigned 1:1 to one of two groups:
- Standard Care: Acetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
- Ibuprofen 400 mg/100 mL NS IV over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL NS at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first.
Patients/surrogates will be approached for consent and randomized upon admission. Therapy will only be initiated once a patient becomes febrile (>=38.3 C, 100.9 F). The use of temperature modulating devices will be permitted as per institutionally approved guidelines in those patients continuing to demonstrate a fever (T>38.3 C, 100.9 F) with either therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Ibuprofen | Experimental | Drug: Intravenous IbuprofenPatients assigned to the ibuprofen treatment group will receive a 400 mg IV ibuprofen bolus over 30 minutes followed by an infusion of ibuprofen at 85 mg/hr. |
| Standard of Care | Other | Drug: Acetaminophen (Standard of Care)Patients assigned to the standard of care group will be given 650 mg of oral acetaminophen and continue to receive 650 mg of oral acetaminophen every 6 hours as needed to maintain temperature < 38.3 C (100.9 F). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older
- Aneurysmal subarachnoid hemorrhage (SAH), Hunt Hess grade >= 3, 24 hours after admission.
- Intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) < 10
- Presence of intraventricular hemorrhage on initial brain computerized tomography (CT) scan
Key exclusion criteria (11 listed)
- Imminent death within 72 hours of admission.
- Plan for discharge from the Neuro intensive care unit (ICU) within 72 hours of admission.
- Diagnosis with sepsis (Systemic inflammatory response syndrome (SIRS) criteria plus the presence of known or suspected infection)
- Presence of coagulopathy (international normalized ratio (INR) > 1.7)
- Thrombocytopenia (platelet count < 100,000)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous IbuprofenAlso: CaldolorIbuprofen 400 mg/100 mL intravenous (IV) over 30 minutes, followed by a continuous infusion of 2000 mg/500 mL at 85 mg/hour (21 mL/hour) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first | Drug | Intravenous Ibuprofen |
| Acetaminophen (Standard of Care)Also: TylenolAcetaminophen 650 mg via oral/nasogastric tube every 6 hours as needed for T>=38.3 C (100.9 F) for up to post bleed day 14 or discharge from the Neuro ICU, whichever comes first. | Drug | Standard of Care |
Primary outcome
Prevalence of Fever Burden
Time frame: Up to14 days
Reduction in fever burden (degrees C x hours) with intravenous ibuprofen infusion as compared to oral acetaminophen over duration of treatment. Fever burden is calculated hourly by subtracting each patient's recorded temperature (from either a bladder or esophageal temperature probe) from 37 degrees C.
3 secondary outcomes
Mean Difference in Inflammatory Markers
Time frame: Up to 14 days
Difference in Cost Between Ibuprofen and Acetaminophen
Time frame: Up to 14 days
Bleeding Incidence
Time frame: Up to 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J. Michael Schmidt, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous Ibuprofen in people with Fever, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of Fever Burden (time frame: Up to14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2017.