Clinical trial NCT02215148: Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients
Official title: Pharmacokinetics and Clinical Response of Tolvaptan in Neurocritical Care Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Brain Injury
Hyponatremia
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Otsuka America Pharmaceutical
name: Medical University of South Carolina
name: Barnes-Jewish Hospital
First posted: 2014-08-13
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population will be comprised of 30 acute brain injury patients in the ICU.

Brief 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


Eligibility criteria: Inclusion Criteria:

1. 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
2. Informed consent obtained from patient or authorized legal representative
3. Age ≥ 18 years

Exclusion Criteria:

1. Use of CYP3A4 inhibitors or inducers as medications, juices, or herbal supplements within 96 hours prior to the study period.
2. A positive urine or serum pregnancy test, or are currently breast-feeding
3. Patients with subarachnoid hemorrhage or in patients suspected to have cerebral salt wasting or any signs of volume depletion
4. Imminent death or brain death
5. Concomitant fungal infection
6. History of HIV
7. Concomitant administration of continuous infusion hypertonic saline, conivaptan or hypertonic saline bolus within 24 hours of study drug administration
8. Diuretic or mannitol administration within 6 hours
9. Serum creatinine ≥ 3.5 mg/dL
10. Diagnosis of cirrhosis or liver function tests \> 2x the upper limit of normal

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) and time to maximum observed plasma concentration (Tmax) of tolvaptan over 36 hours post-dose
timeFrame: Over 36 hours from drug administration
measure: The elimination rate constant (ke) of tolvaptan over 36 hours post-dose
timeFrame: Over 36 hours from drug administration
measure: Area under the plasma concentration time curve (AUC) of tolvaptan from time zero to 36 hours post-dose
timeFrame: Over 36 hours from drug administration
Secondary outcomes:
measure: The clinical response of tolvaptan administered through the nasogastric tube in acute brain injured patients
timeFrame: Over 36 hours from drug administration
measure: The safety of tolvaptan administered via a nasogastric tube in acute brain injured patients
timeFrame: Over 36 hours from drug administration
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kathryn A Morbitzer, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Denise H. Rhoney, PharmD
role: PRINCIPAL_INVESTIGATOR
References: