The Routine Use of SSRI's at the Initiation of End-stage Renal Disease Treatment (RoSIE) (RoSIE)

A Pilot Study to Evaluate the Feasibility and Safety of Performing a Double Blind, Placebo-controlled, Randomized Controlled Trial of the Routine Use of SSRI's at the Initiation of End-stage Renal Disease Treatment

In this study the investigators hypothesize that antidepressant therapy may improve the overall welling of patients with acute or chronic kidney disease when given around the time of starting chronic dialysis therapy. This study is a pilot, randomized controlled trial that aims to examine whether prescribing oral escitalopram to all incident dialysis patients is safe and feasible.

Study Overview

• Status: Terminated
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Escitalopram; Drug: Placebo

Detailed Description

Over 120,000 people with kidney disease start chronic dialysis therapy across North America each year. In addition to high mortality, studies uniformly report high rates of depression, pain and non-specific symptoms after dialysis is started. Suicide rates are high, particularly early in the treatment history, and withdrawal from dialysis is increasingly common in recent years, suggesting a high burden of depressive symptoms. While various treatments appear to be effective, there are multiple barriers preventing patients from getting or accepting appropriate care for depression. The investigators hypothesize that antidepressant therapy may improve morbidity and mortality when prescribed to patients with acute or chronic kidney disease (CKD) around the time of starting chronic dialysis therapy.

This is a phase II, multi-centre, double blind, randomized controlled trial to compare the safety and feasibility of oral escitalopram to placebo in incident dialysis patients. Those who have started chronic dialysis therapy within 12 weeks of being identified will be eligible for the study. Participants will randomized 1:1 to receive either escitalopram or placebo daily for 26 weeks.

The primary outcome is feasibility in terms of recruitment rates and protocol compliance. The secondary outcomes include estimates of safety (adverse events) and efficacy (hospitalization days, mortality, and changes in depression and quality of life scores). This pilot trial is intended to guide and inform the design of a full scale study to evaluate whether the routine use of escitalopram can improve the quality of life and hospital free days in patients on dialysis, as compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M6G 2K8
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female aged ≥ 25 years
2. Patient or substitute decision maker willing and able to give informed consent
3. Incident to dialysis defined as within a 12-week window from the first dialysis treatment (1 week prior to, to 11 weeks after). Patients on all forms of dialysis except CRRT (including peritoneal dialysis, home hemodialysis, in-centre intermittent hemodialysis and nocturnal dialysis) will be eligible. Patients returning to dialysis after transplant graft loss will be eligible.

Exclusion Criteria:

1. Past history of allergy to, or intolerance of, escitalopram
2. Known severe hepatic dysfunction
3. Recent history of active bleeding within the past 3 months (e.g. gastrointestinal bleeding requiring hospitalization) or known bleeding disorder
4. Current use of class I anti-arrhythmic medications; SSRI or SNRI antidepressants; pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine or methyldopa, omeprazole; tri-cyclic and tetra-cyclic anti-depressants, neuroleptics or anti-convulsants, triptans, tramadol, linezolid, tryptophan, and St. John's Wort; but not gabapentin
5. Past treatment failure for depression with escitalopram or with ≥ 2 antidepressant treatments of at least 6 weeks duration each
6. Initiation of psychotherapy for depression in the 3 months prior to study entry
7. Alcohol or substance abuse or dependence that requires acute detoxification at study entry
8. Present or past psychosis or bipolar disorder, schizophrenia or any other psychotic disorder documented in medical records
9. Suicidal ideation defined as the patient is at significant risk of suicide on the Columbia Suicide Scale71 or has attempted suicide within 6 months prior to the Screening Visit
10. Clinically-identified major depressive disorder that, in the opinion of the clinical team, requires treatment
11. Pregnancy, lactation and women of childbearing potential not using adequate contraception
12. Abnormal QTc at baseline: QTcF interval >600 ms (based on the Fredericia correction where QTcF = QT/RR0.33)66
13. Lactose intolerance (as placebo contains lactose)
14. Known uncontrolled glaucoma
15. Patients requiring treatment with continuous renal replacement therapy (CRRT)
16. Documented history of brain tumour

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The matching placebo will be up-titrated and down-titrated at the same time intervals as the active medication.
Active Comparator: Escitalopram	Drug: Escitalopram; Dose will be initiated at 5 mg daily. At two weeks, a safety and tolerability assessment will be performed, and if tolerated, the dose will be increased to 10 mg daily. At 24 weeks, the medication will be titrated downwards to 5 mg daily for a further two weeks before discontinuation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of consecutive incident dialysis patients that are eligible		12 months
Proportion of eligible patients that will consent to randomization		12 months
Proportion of randomized patients that comply with their group assignment	Compliance defined as >80% of doses taken	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Death	12 months
Serious adverse events	12 months
Number of patients withdrawn from the study drug due to QTc prolongation	12 months
Completion rate for all secondary outcome measures (KDQoL, HUI-III, PHQ-9, Handgrip and 2-Minute Walk Test)	3 months and 6 months
Hospital-free days	12 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: McMaster University; Unity Health Toronto; University of Toronto

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 30, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 9, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Renal Insufficiency, Chronic; Hemodialysis; Kidney Failure; Peritoneal Dialysis; Depressive Symptoms; Escitalopram; Antidepressants; Selective Serotonin Reuptake Inhibitors; Dialysis, Renal; Controlled Clinical Trials, Randomized
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: 01 (Miami VAHS)