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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female aged ≥ 25 years Patient or substitute decision maker willing and able to give informed consent 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: Past history of allergy to, or intolerance of, escitalopram Known severe hepatic dysfunction Recent history of active bleeding within the past 3 months (e.g. gastrointestinal bleeding requiring hospitalization) or known bleeding disorder 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 Past treatment failure for depression with escitalopram or with ≥ 2 antidepressant treatments of at least 6 weeks duration each Initiation of psychotherapy for depression in the 3 months prior to study entry Alcohol or substance abuse or dependence that requires acute detoxification at study entry Present or past psychosis or bipolar disorder, schizophrenia or any other psychotic disorder documented in medical records 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 Clinically-identified major depressive disorder that, in the opinion of the clinical team, requires treatment Pregnancy, lactation and women of childbearing potential not using adequate contraception Abnormal QTc at baseline: QTcF interval >600 ms (based on the Fredericia correction where QTcF = QT/RR0.33)66 Lactose intolerance (as placebo contains lactose) Known uncontrolled glaucoma Patients requiring treatment with continuous renal replacement therapy (CRRT) Documented history of brain tumour

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram<br> | Drug: Escitalopram<br>* 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.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* The matching placebo will be up-titrated and down-titrated at the same time intervals as the active medication.<br>|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Death |  | 12 months | 
| Hospital-free days |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Controlled Clinical Trials, Randomized, Kidney Failure, Renal Insufficiency, Chronic, Dialysis, Renal, Peritoneal Dialysis, Depressive Symptoms, Selective Serotonin Reuptake Inhibitors, Antidepressants, Escitalopram