Clinical trial NCT02407821: The Routine Use of SSRI's at the Initiation of End-stage Renal Disease Treatment (RoSIE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: End Stage Renal Disease
Keywords: Controlled Clinical Trials, Randomized
Kidney Failure
Renal Insufficiency, Chronic
Dialysis, Renal
Peritoneal Dialysis
Hemodialysis
Depressive Symptoms
Selective Serotonin Reuptake Inhibitors
Antidepressants
Escitalopram
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: McMaster University
name: Unity Health Toronto
name: University of Toronto
First posted: 2015-04-03
Enrollment: 25
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of consecutive incident dialysis patients that are eligible
timeFrame: 12 months
measure: Proportion of eligible patients that will consent to randomization
timeFrame: 12 months
measure: Proportion of randomized patients that comply with their group assignment
timeFrame: 12 months
Secondary outcomes:
measure: Serious adverse events
timeFrame: 12 months
measure: Number of patients withdrawn from the study drug due to QTc prolongation
timeFrame: 12 months
measure: Completion rate for all secondary outcome measures (KDQoL, HUI-III, PHQ-9, Handgrip and 2-Minute Walk Test)
timeFrame: 3 months and 6 months
measure: Death
timeFrame: 12 months
measure: Hospital-free days
timeFrame: 12 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Vanita Jassal, MD
role: PRINCIPAL_INVESTIGATOR
References: