Regional Tolvaptan Registry (Tolvaptan)

Low blood sodium is a common observation in patients presenting with heart failure and is associated with increased mortality, prolonged hospital stay, and repeat hospital visits. Tolvaptan is a new and approved medication to treat low sodium levels in patients who present with symptoms of heart failure, however, it is not currently available as a treatment option due to high costs not covered by our provincial plan. In this observational, non-randomized study the drug will be provided to all subjects free of charge and given only during their hospital stay. After discharge subjects will be followed for 6 months (3 visits).

Study Overview

• Status: Unknown
• Conditions: Hyponatremia; Decompensated Heart Failure
• Intervention / Treatment: Drug: Tolvaptan; Other: No intervention

Detailed Description

Purpose: A prospective, open-label, real life registry of Tolvaptan in hospitalized heart failure patients with hyponatremia.

Hypothesis: Administration of Tolvaptan in hospitalized patients with heart failure and hyponatremia will demonstrate improvements in patient symptom status and cost savings from decreased healthcare utilization.

Justification: In clinical trials, Tolvaptan has been shown to quickly, effectively, and safely improve sodium levels in heart failure patients, and decrease the length of hospital stay and improve symptom status compared to placebo. Although Tolvaptan is an approved drug in Canada for the treatment of patients hospitalized with heart failure and hyponatremia, its availability is limited to private buyers and not available on hospital formularies due to cost constraints. There are no alternatives to this first in class agent.

Objectives: The primary endpoint is reduction in length of stay for heart failure in registry participants compared to length of stay in the Vancouver Coastal Health (VCH) administrative data set. Secondary endpoints will include recurrent hospitalization, change in quality of life, and B-type Natriuretic Peptide (BNP) levels over the study period.

Research Method: Patients admitted to Vancouver General Hospital (VGH) with heart failure and hyponatremia will be identified through clinical referral by cardiologists who have ensured that all other measures have been undertaken to improve the patient's clinical status.

Tolvaptan is dispensed according to product monograph and clinician discretion, and will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge. Bloodwork will be drawn to monitor liver function and electrolytes during hospitalization and in follow up. Data will be captured from time of consent until 6 months after hospital discharge.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Andrew Starovoytov, MD, CCRP; Phone Number: 604-875-5079; Email: a.starovoytov@ubc.ca
• Study Contact Backup: Name: Melissa Bedford, BSc; Phone Number: 604-875-5120; Email: melissa.bedford@vch.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver General Hospital
      • Contact: Andrew Starovoytov, MD, CCRP; Phone Number: 604-875-5079; Email: a.starovoytov@ubc.ca
      • Contact: Melissa Bedford, BSc; Phone Number: 604-875-5120; Email: melissa.bedford@vch.ca
      • Principal Investigator: Sean Virani, MD, MSc, MPH, FRCPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient has clinical evidence of heart failure AND elevated BNP or evidence of left ventricular dysfunction (left ventricular ejection fraction (LVEF) < 40%) on diagnostic imaging.
2. Serum sodium < 130 mmol/L OR serum sodium 131-134 mmol/L and symptomatic.
3. Sodium and fluid restriction ongoing.
4. Trial of optimal diuretic therapy (at prescribing physician's clinical discretion).
5. Discontinuation of non-essential medications/treatments that are known to cause hyponatremia.

Exclusion Criteria:

1. Life expectancy < 6 months
2. Documented adverse events with tolvaptan in the past

3. Meet exclusion criteria from the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT Trial):

   • Serum sodium < 120mmol/L if neurologic impairment
   • Confounding disease (e.g. recent stroke or myocardial infarction (MI), recent surgery, uncontrolled diabetes, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group; Administration of oral tolvaptan (15-60mg PO titration) during admission for decompensated heart failure	Drug: Tolvaptan; Tolvaptan is dispensed during hospitalization according to its product monograph and clinician discretion. It will be discontinued once serum sodium is normalized, or in the case of a drug related adverse event or hospital discharge.; Other Names: Samsca
Other: Control group; There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority	Other: No intervention; There is no intervention planned for the Control group. Aggregate administrative regional data describing patient outcomes from the local health authority will be used as a comparator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay	Hospital length of stay for heart failure in the treatment group will be measured as days and compared to administrative regional data describing patient outcomes from the local health authority.	Subjects are followed for 6 months after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent hospitalization.	This will be measured by the number of times a patient is readmitted to hospital following their discharge from the initial hospitalization.	Subjects are followed for 6 months after discharge
Change in quality of life.	This will be assessed by administrating the Minnesota Living with Heart Failure questionnaire at initial hospitalization, 1 month follow-up, 3 month follow-up, and 6 month follow-up timepoints.	Subjects are followed for 6 months after discharge
BNP (Brain-Type Natriuretic Peptide) levels	BNP is an established biomarker of CHF severity and blood samples will be collected at 1, 3, and 6 month visits. Values will be collected as a continuous variable.	Subjects are followed for 6 months after discharge

Collaborators and Investigators

• Sponsor: Cardiology Research UBC
• Investigators: Principal Investigator: Sean Virani, MD, MSc, MPH, FRCPC, Director of the Heart Failure and Cardiology-Oncology Programs at VGH

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: January 14, 2016
• First Submitted That Met QC Criteria: January 25, 2016
• First Posted (Estimate): January 28, 2016

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Tolvaptan
• Other Study ID Numbers: H15-00115

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED