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

NCT ID: NCT02407821

Last Updated: 2018-10-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2017-01-31

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.

Conditions

End Stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Escitalopram

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The matching placebo will be up-titrated and down-titrated at the same time intervals as the active medication.

Interventions

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.

Intervention Type: DRUG

Placebo

The matching placebo will be up-titrated and down-titrated at the same time intervals as the active medication.

Intervention Type: DRUG

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

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: collaborator

University of Toronto

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vanita Jassal, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

01

Identifier Type: -

Identifier Source: org_study_id