Brain InjuryNCT02215148
Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients
An observational study of Brain Injury and Hyponatremia, run by University of North Carolina, Chapel Hill at 3 sites in United States.
Trial summary
To assess the pharmacokinetic profile of tolvaptan in critically ill acute brain injury patients and to secondarily evaluate the clinical response and safety of tolvaptan in acute brain injured patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Injury, Hyponatremia
- What is being tested?
- Tolvaptan
- How many people
- 1 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2014to Aug 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: The population will be comprised of 30 acute brain injury patients in the ICU.
Who may be able to join
- Acute brain injury patients in the ICU with hyponatremia (Na < 135 mmol/L) necessitating treatment in addition to fluid restriction per clinical judgement or patients at risk for worsening cerebral edema
- Informed consent obtained from patient or authorized legal representative
- Age ≥ 18 years
Who cannot join
- Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period.
- A positive urine or serum pregnancy test, or are currently breast-feeding
- Patients with subarachnoid hemorrhage or in patients suspected to have cerebral salt wasting or any signs of volume depletion
- Imminent death or brain death
- Concomitant fungal infection
- History of HIV
Show all 10Show fewer
- Concomitant administration of continuous infusion hypertonic saline, conivaptan or hypertonic saline bolus within 24 hours of study drug administration
- Diuretic or mannitol administration within 6 hours
- Serum creatinine ≥ 3.5 mg/dL
- Diagnosis of cirrhosis or liver function tests > 2x the upper limit of normal
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Barnes-Jewish Hospital
St Louis, Missouri, 63110
About this study
To assess the pharmacokinetic profile of tolvaptan in critically ill acute brain injury patients and to secondarily evaluate the clinical response and safety of tolvaptan in acute brain injured patients
- Conditions
- Brain Injury, Hyponatremia
- Being tested
- Tolvaptan
- Medical subject headings
- Brain Injuries, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
| Study group | Role | What they receive |
|---|---|---|
| Brain injured patients with hyponatremia | Patients with acute brain injury who develop hyponatremia and are administered tolvaptan via the nasogastric tube, deemed necessary by the primary medical team. Receives: Drug: Tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose
Cmax will be derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Measured: Over 36 hours from drug administration
The elimination rate constant (ke) of tolvaptan over 36 hours post-dose
Ke derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Measured: Over 36 hours from drug administration
Area under the plasma concentration time curve (AUC) of tolvaptan from time zero to 36 hours post-dose
AUC will be computed from 0 to 36 hours using the linear-log trapezoidal method and extrapolated to infinity. Tolvaptan concentrations will be determined using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Measured: Over 36 hours from drug administration
Secondary outcomes (2)
The clinical response of tolvaptan administered through the nasogastric tube in acute brain injured patients
Clinical response is defined as a change in serum sodium of 4 - 6 mEq/L
Measured: Over 36 hours from drug administration
The safety of tolvaptan administered via a nasogastric tube in acute brain injured patients
Safety assessments will include: vital signs, clinical laboratory tests, concomitant medications, and reported or observed adverse events. The rate of sodium correction will also be assessed. Excessive correction in sodium is defined as ≥ 12 mE/L increased in serum sodium within 24 hours of the dose. Excessive drop in blood pressure will be defined as >20% reduction in MAP from baseline.
Measured: Over 36 hours from drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study startNov 2014
- Primary completionAug 2016
- Study completionAug 2016
Why it stopped: Slow subject enrollment and contracting issues; sponsor decided to abort study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka America Pharmaceutical, Medical University of South Carolina, Barnes-Jewish Hospital
- Responsible party
- Sponsor
- Investigators
- Kathryn A Morbitzer, PharmD, Principal investigator, University of North Carolina, Chapel HillDenise H. Rhoney, PharmD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02215148
- Sponsor's protocol ID
- 13-3991
- Other IDs
- 20141663
- Status last verified
- Sep 2016
- First submitted
- 11 Aug 2014
- Last updated
- 8 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients
- ClinicalTrials.gov ID
- NCT02215148
- Acronym / sponsor ID
- 13-3991
- Conditions
- Brain Injury, Hyponatremia
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slow subject enrollment and contracting issues; sponsor decided to abort study
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Otsuka America Pharmaceutical, Medical University of South Carolina, Barnes-Jewish Hospital
- Study start
- Nov 2014
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the pharmacokinetic profile of tolvaptan in critically ill acute brain injury patients and to secondarily evaluate the clinical response and safety of tolvaptan in acute brain injured patients
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brain injured patients with hyponatremia | – | Drug: TolvaptanPatients with acute brain injury who develop hyponatremia and are administered tolvaptan via the nasogastric tube, deemed necessary by the primary medical team. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The population will be comprised of 30 acute brain injury patients in the ICU.
Key inclusion criteria (3 listed)
- Acute brain injury patients in the ICU with hyponatremia (Na < 135 mmol/L) necessitating treatment in addition to fluid restriction per clinical judgement or patients at risk for worsening cerebral edema
- Informed consent obtained from patient or authorized legal representative
- Age ≥ 18 years
Key exclusion criteria (10 listed)
- Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period.
- A positive urine or serum pregnancy test, or are currently breast-feeding
- Patients with subarachnoid hemorrhage or in patients suspected to have cerebral salt wasting or any signs of volume depletion
- Imminent death or brain death
- Concomitant fungal infection
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 |
|---|---|---|
| Tolvaptan | Drug | Brain injured patients with hyponatremia |
Primary outcome
Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose
Time frame: Over 36 hours from drug administration
Cmax will be derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
The elimination rate constant (ke) of tolvaptan over 36 hours post-dose
Time frame: Over 36 hours from drug administration
Ke derived from plasma concentrations versus time using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
Area under the plasma concentration time curve (AUC) of tolvaptan from time zero to 36 hours post-dose
Time frame: Over 36 hours from drug administration
AUC will be computed from 0 to 36 hours using the linear-log trapezoidal method and extrapolated to infinity. Tolvaptan concentrations will be determined using a validated LS/MS/MS assay is sodium heparinized plasma. The tolvaptan assay has a range of 1.00 - 200 mg/mL. Blood samples will be collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30 and 36 hours after the dose of tolvaptan is administered. The first 15 patients will receive single dose 15mg of tolvaptan via a gastric tube and if determined not bioequivalent and no clinical response to oral administration and safe to administer, then last 15 patients will receive 30mg single dose via a gastric tube.
2 secondary outcomes
The clinical response of tolvaptan administered through the nasogastric tube in acute brain injured patients
Time frame: Over 36 hours from drug administration
The safety of tolvaptan administered via a nasogastric tube in acute brain injured patients
Time frame: Over 36 hours from drug administration
Results and safety
The study was stopped early (reason given: Slow subject enrollment and contracting issues; sponsor decided to abort study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2016.
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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.
Kathryn A Morbitzer, PharmD principal investigator
University of North Carolina, Chapel Hill
Denise H. Rhoney, PharmD principal investigator
University of North Carolina, Chapel Hill
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Injury and Hyponatremia, run by University of North Carolina, Chapel Hill at 3 sites 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 3 inclusion and 10 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 8 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
The study was stopped early (reason given: Slow subject enrollment and contracting issues; sponsor decided to abort study). Results are not available in the source record.
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?
Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose (time frame: Over 36 hours from drug administration). The study lists 3 primary outcomes in all. 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 8 Sep 2016.