NCT02545114

Brief Summary

Hyponatremia occurs frequently in patients with acute brain injury in the days to weeks following injury, and may contribute to adverse outcome. In addition, hyponatremia can aggravate neurologic dysfunction, complicate neurological assessments, and contribute to neurologic symptoms such as gait dysfunction that can impair efforts at mobilization and rehabilitation. Strict normonatremia (serum Na levels between 135 and 145 meq/dl) is the goal in most patients with acute brain injury. SIADH is the most frequent cause of hyponatremia in patients with neurological injury; however, treatment with fluid restriction is often difficult or contra-indicated, for example in patients with subarachnoid hemorrhage (SAH) where intravascular hypovolemia can trigger vasospasms. The aim of this project is to test Tolvaptan, an ADH antagonist, as a treatment in selected patients with acute brain injury who have developed SIADH.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Aug 2015

Geographic Reach
1 country

2 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

September 2, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 9, 2015

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2016

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2016

Completed
Last Updated

September 24, 2018

Status Verified

September 1, 2015

Enrollment Period

11 months

First QC Date

September 2, 2015

Last Update Submit

September 20, 2018

Conditions

HyponatremiaSIADH

Keywords

HyponatremiaSIADH, strokeSAH; ICHAIS

Outcome Measures

Primary Outcomes (1)

  • Serum sodium level

    1-3 days

Secondary Outcomes (3)

  • Incidence of vasospasms

    3 weeks

  • Incidence of pulmonary edema

    2 weeks

  • Length of stay in ICU

    4 weeks

Study Arms (1)

Tolvaptan

OTHER

Intervention arm. Open label, no control group

Drug: Tolvaptan

Interventions

TolvaptanDRUG

Use of Tolvaptan to treat SIADH-induced hyponatremia in selected patients with acute neurological injuries.

Also known as: Samsca
Tolvaptan

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with euvolemic or hypervolemic hyponatremia: serum Na \<135 meq/dl
  • Inappropriately high urinary sodium excretion

You may not qualify if:

  • Clinically evident hypovolemic hyponatremia
  • Recent myocardial infarction or cardiac surgery
  • Sustained ventricular tachycardia or fibrillation
  • Systolic blood pressure of less than 90 mm Hg
  • Serum creatinine concentration of more than 3 mg per deciliter
  • History of, or biochemical evidence of, liver disease
  • Serum sodium concentration less than 120 mmol per liter in association with neurologic impairment
  • Urinary tract obstruction
  • Use of other diuretics (furosemide, burinex, hydrochlorthiazide) that cannot be safely discontinued
  • Concomitant use of hypertonic saline (prior use OK, if hypertonic is stopped within 1 hour of the first dose of Tolvaptan administration).
  • History of chronic SIADH or known chronic hyponatremia from other causes (e.g. heart failure)
  • Uncontrolled hypothyroidism or adrenal insufficiency
  • Severe co-morbidities with life expectancy \<6 months
  • CMO status

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (12)

  • Hannon MJ, Behan LA, O'Brien MM, Tormey W, Ball SG, Javadpour M, Sherlock M, Thompson CJ. Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting. J Clin Endocrinol Metab. 2014 Jan;99(1):291-8. doi: 10.1210/jc.2013-3032. Epub 2013 Dec 20.

    PMID: 24248182BACKGROUND

  • Rahman M, Friedman WA. Hyponatremia in neurosurgical patients: clinical guidelines development. Neurosurgery. 2009 Nov;65(5):925-35; discussion 935-6. doi: 10.1227/01.NEU.0000358954.62182.B3.

    PMID: 19834406BACKGROUND

  • Sherlock M, O'Sullivan E, Agha A, Behan LA, Owens D, Finucane F, Rawluk D, Tormey W, Thompson CJ. Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients. Postgrad Med J. 2009 Apr;85(1002):171-5. doi: 10.1136/pgmj.2008.072819.

    PMID: 19417163BACKGROUND

  • Sherlock M, O'Sullivan E, Agha A, Behan LA, Rawluk D, Brennan P, Tormey W, Thompson CJ. The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2006 Mar;64(3):250-4. doi: 10.1111/j.1365-2265.2006.02432.x.

    PMID: 16487432BACKGROUND

  • Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, Hanggi D, Hoh BL, Lanzino G, Le Roux P, Rabinstein A, Schmutzhard E, Stocchetti N, Suarez JI, Treggiari M, Tseng MY, Vergouwen MD, Wolf S, Zipfel G; Neurocritical Care Society. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care. 2011 Sep;15(2):211-40. doi: 10.1007/s12028-011-9605-9.

    PMID: 21773873BACKGROUND

  • Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G; European Stroke Organization. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35(2):93-112. doi: 10.1159/000346087. Epub 2013 Feb 7.

    PMID: 23406828BACKGROUND

  • Edlow JA, Samuels O, Smith WS, Weingart SD. Emergency neurological life support: subarachnoid hemorrhage. Neurocrit Care. 2012 Sep;17 Suppl 1:S47-53. doi: 10.1007/s12028-012-9761-6.

    PMID: 22932990BACKGROUND

  • Stocchetti N; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Triggers for aggressive interventions in subarachnoid hemorrhage. Neurocrit Care. 2011 Sep;15(2):324-8. doi: 10.1007/s12028-011-9597-5.

    PMID: 21748498BACKGROUND

  • Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3.

    PMID: 23121377BACKGROUND

  • Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C; SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16;355(20):2099-112. doi: 10.1056/NEJMoa065181. Epub 2006 Nov 14.

    PMID: 17105757BACKGROUND

  • Berl T, Quittnat-Pelletier F, Verbalis JG, Schrier RW, Bichet DG, Ouyang J, Czerwiec FS; SALTWATER Investigators. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr;21(4):705-12. doi: 10.1681/ASN.2009080857. Epub 2010 Feb 25.

    PMID: 20185637BACKGROUND

  • Polderman KH, Bajus D, Varon J. Use of Tolvaptan to treat SIADH-induced hyponatremia in selected patients with acute neurological injuries. Neurocrit Care 2014 21:S224 (abstract 215).

    BACKGROUND

MeSH Terms

Conditions

HyponatremiaInappropriate ADH SyndromeStrokeHepatitis, Infectious Canine

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Water-Electrolyte ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesPituitary DiseasesHypothalamic DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesEndocrine System DiseasesCerebrovascular DisordersVascular DiseasesCardiovascular DiseasesHepatitis, Viral, AnimalHepatitis, AnimalInfectionsAdenoviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitisLiver DiseasesDigestive System DiseasesDog DiseasesAnimal Diseases

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Kees Polderman, MD, PhD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDIV
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 2, 2015

First Posted

September 9, 2015

Study Start

August 1, 2015

Primary Completion

July 1, 2016

Study Completion

September 1, 2016

Last Updated

September 24, 2018

Record last verified: 2015-09

Locations

US(2)