Tolvaptan Versus Fluid Restriction in SIADH

NCT04119206 | Completed

• 1 other identifier: Tolvaptan
• Study Type: observational
• Target: 334
• Locations: 0 countries
• Sites: N/A

Brief Summary

Context. The relevance of hyponatremia has been acknowledged by guidelines from the United States of America (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. Objective. In hyponatremia following pituitary surgery - caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion - the investigators compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and moderate dose. Design. Prospective observational study. Setting. Neurosurgical Department of a University hospital with more 200 pituitary procedures per year. Patients. Participants undergoing surgery for sellar lesions and developing a serum sodium below 135 mmol/L. The diagnosis of SIADH was established by eu- or hypervolemia (daily measurement of body weight and fluid balance daily), an inappropriately concentrated urine (specific gravity) and exclusion of a cortico- and thyreotropic insufficiency. Intervention. Participants were treated with fluid restriction (n=38) or tolvaptan at 3.75 (n=38) or 7.5 mg (n=48) orally. Main Outcome Measures. Treatment efficacy was assessed by the duration of hyponatremia, sodium nadir and length of hospitalization. Safety was established by an increment serum sodium below 10 mmol/L per day and exclusion of side effects.

Conditions

Hyponatremia; Syndrome of Inappropriate ADH (SIADH) Secretion; Pituitary

Keywords

hyponatremia; vasopressin; anti-diuretic hormone; fluid restriction; tolvaptan; pituitary surgery

Outcome Measures

Primary Outcomes (4)

• Mean serum sodium concentration

  Postoperative mean serum sodium

  Day 1 post-op up to 15 days

• Serum sodium nadir concentration

  Postoperative serum sodium nadir

  Day 1 post-op up to 15 days

• Number of days with serum sodium concentration below 136mmol/L

  No. of postoperative days serum sodium was below 136mmol/L

  Day 1 post-op up to 15 days

• Number of days with serum sodium concentration below 133mmol/L

  No. of postoperative days serum sodium was below 133mmol/L

  Day 1 post-op up to 15 days

Secondary Outcomes (3)

• Number of events with mild serum sodium overcorrection

  Day 1 post-op up to 15 days

• Number of events with severe serum sodium overcorrection

  Day 1 post-op up to 15 days

• Number of days in the hospital

  Up to 1 month

Study Arms (4)

Control

Normonatremic control, no intervention.

Fluid restriction

Hyponatremic patients (serum sodium \<135mmol/L): restriction of fluid intake \< 1L

Tolvaptan 3.75mg

Hyponatremic patients (serum sodium \<135mmol/L): tolvaptan 3.75 mg tablet; The serum sodium concentration was controlled at 6:00 pm. Those patients, whose serum sodium concentration further dropped below 132 mmol/L, were treated with a second tablet of tolvaptan and the serum sodium was measured the next day at 8:00 am. Those patients, whose serum sodium was increased by not more than 5 mmol/L underwent the next blood check on the next day at 8:00 am. Those patients, whose serum sodium increased by more than 5 mmol/L were treated by 1L tea/water or a 500 mL 5% glucose infusion.

Tolvaptan 7.5mg

Hyponatremic patients (serum sodium \<135mmol/L): tolvaptan 7.5 mg tablet; The serum sodium concentration was controlled at 6:00 pm. Those patients, whose serum sodium concentration further dropped below 132 mmol/L, were treated with a second tablet of tolvaptan and the serum sodium was measured the next day at 8:00 am. Those patients, whose serum sodium was increased by not more than 5 mmol/L underwent the next blood check on the next day at 8:00 am. Those patients, whose serum sodium increased by more than 5 mmol/L were treated by 1L tea/water or a 500 mL 5% glucose infusion.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients of the Department of Neurosurgery, University of Erlangen-Nuremberg, undergoing surgery for sellar lesions were prospectively included.

You may qualify if:

• Informed written consent was given by the participant or the next-of-kin.

You may not qualify if:

• Age below 18 years Pregnancy Tolvaptan intolerance.

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

MeSH Terms

Conditions

Hyponatremia; Inappropriate ADH Syndrome; Pituitary Diseases; Diabetes Insipidus

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 8, 2019
• Study Start: January 1, 2009
• Primary Completion: December 31, 2013
• Study Completion: December 31, 2013
• Last Updated: October 8, 2019

Record last verified: 2019-10