Hyponatremia Clinical Trial
Official title:
Use of Tolvaptan to Treat SIADH-induced Hyponatremia in Selected Patients With Acute Neurological Injuries
NCT number | NCT02545114 |
Other study ID # | 0002103 |
Secondary ID | |
Status | Terminated |
Phase | N/A |
First received | |
Last updated | |
Start date | August 2015 |
Est. completion date | September 2016 |
Verified date | September 2015 |
Source | Polderman, Kees, H., MD, PhD |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Terminated |
Enrollment | 25 |
Est. completion date | September 2016 |
Est. primary completion date | July 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Patients with euvolemic or hypervolemic hyponatremia: serum Na <135 meq/dl - Inappropriately high urinary sodium excretion Exclusion Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
United States | Mercy Hospital | Pittsburgh | Pennsylvania |
United States | UPMC Presbyterian | Pittsburgh | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Polderman, Kees, H., MD, PhD | University of Pittsburgh |
United States,
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. Erratum in: J Am Soc Nephrol. 2010 Aug;21(8):1407. — View Citation
Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, Hänggi 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. Review. — View Citation
Edlow JA, Samuels O, Smith WS, Weingart SD. Emergency neurological life support: subarachnoid hemorrhage. Neurocrit Care. 2012 Sep;17 Suppl 1:S47-53. Review. — View Citation
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. Erratum in: J Clin Endocrinol Metab. 2014 Mar;99(3):1096. Javadpur, M [corrected to Javadpour, M]. — View Citation
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).
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. Review. — View Citation
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. Epub 2006 Nov 14. — View Citation
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. — View Citation
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. — View Citation
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. Review. — View Citation
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. — View Citation
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. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Serum sodium level | 1-3 days | ||
Secondary | Incidence of vasospasms | 3 weeks | ||
Secondary | Incidence of pulmonary edema | 2 weeks | ||
Secondary | Length of stay in ICU | 4 weeks |
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