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Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST).

ABSTRACT: Major Depressive Disorder (MDD) affects one in five patients with Chronic Kidney Disease (CKD) and is an independent risk factor for hospitalization and death before and after dialysis initiation. However, it remains an under-recognized and under-treated problem, in part due to the lack of well-controlled studies that support or refute the efficacy and safety of antidepressant medications in CKD patients. Major trials of antidepressant treatment excluded patients with stages 3-5 CKD, precisely those at higher risk for both depression and increased mortality. The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) is a randomized, double-blinded, placebo-controlled trial of sertraline, a selective serotonin reuptake inhibitor (SSRI). It will enroll 200 adults with stages 3-5 CKD and MDD excluding kidney transplant and chronic dialysis patients. Sertraline will be administered at an initial dose of 50mg once daily or matching placebo followed by a dose escalation strategy consisting of 50mg increments at 2week intervals (as tolerated) to a maximum dose of 200mg. The primary outcome is improvement in depression symptom severity measured by the Quick Inventory of Depressive Symptomatology scale. Secondary outcomes include safety endpoints and improvement in quality of life. Changes in cognitive function, adherence to medications, nutritional status, inflammation, and platelet function will be explored as potential mechanisms by which depression may mediate poor outcomes. We discuss the rationale and design of the CAST study, the largest placebo-controlled trial aimed to establish safety and efficacy of a SSRI in the acute phase treatment of CKD patients with MDD.

SUBMITTER: Jain N

PROVIDER: S-EPMC3525806 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST).

Jain Nishank N Trivedi Madhukar H MH Rush A John AJ Carmody Thomas T Kurian Benji B Toto Robert D RD Sarode Ravindra R Hedayati S Susan SS

Contemporary clinical trials 20121022 1

Major Depressive Disorder (MDD) affects one in five patients with Chronic Kidney Disease (CKD) and is an independent risk factor for hospitalization and death before and after dialysis initiation. However, it remains an under-recognized and under-treated problem, in part due to the lack of well-controlled studies that support or refute the efficacy and safety of antidepressant medications in CKD patients. Major trials of antidepressant treatment excluded patients with stages 3-5 CKD, precisely t ...[more]

PMID: 23085503

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Project description:ImportanceMajor depressive disorder (MDD) is prevalent among patients with chronic kidney disease (CKD) and is associated with morbidity and mortality. The efficacy and adverse events of selective serotonin reuptake inhibitors in these patients are unknown.ObjectiveTo determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD.Design, setting, and participantsThe Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) was a randomized, double-blind, placebo-controlled trial involving 201 patients with stage 3, 4, or 5 non-dialysis-dependent CKD, who were enrolled at 3 US medical centers. The Mini Neuropsychiatric Interview was used to establish MDD. The first participant was randomized in March 2010 and the last clinic visit occurred in November 2016.InterventionsAfter a 1-week placebo run-in, participants were randomized to sertraline (n = 102) for 12 weeks at an initial dose of 50 mg/d (escalated to a maximum dose of 200 mg/d based on tolerability and response) or matching placebo (n = 99).Main outcomes and measuresThe primary outcome was improvement in depressive symptom severity from baseline to 12 weeks determined by the 16-item Quick Inventory of Depression Symptomatology-Clinician Rated (QIDS-C16) (score range, 0-27; minimal clinically important difference, 2 points). Secondary outcomes included improvement in quality of life (Kidney Disease Quality of Life Survey-Short Form; score range, 0-100; higher scores indicate more favorable quality of life) and adverse events.ResultsThere were 201 patients (mean [SD] age, 58.2 [13.2] years; 27% female) randomized. The primary analysis included 193 patients who had at least 1 outcome assessment after randomization. The mean (SD) baseline QIDS-C16 score was 14.0 (2.4) in the sertraline group (n = 97) and 14.1 (2.4) in the placebo group (n = 96). The median participation time was 12.0 weeks and the median achieved dose was 150 mg/d, which was not significantly different between the groups. The QIDS-C16 score changed by -4.1 in the sertraline group and by -4.2 in the placebo group (between-group difference, 0.1 [95% CI, -1.1 to 1.3]; P = .82). There was no significant between-group difference in change in patient-reported overall health on the Kidney Disease Quality of Life Survey (median score, 0 in the sertraline group vs 0 in the placebo group; between-group difference, 0 [95% CI, -10.0 to 0]; P = .61). Nausea or vomiting occurred more frequently in the sertraline vs placebo group (22.7% vs 10.4%, respectively; between-group difference, 12.3% [95% CI, 1.9% to 22.6%], P = .03), as well as diarrhea (13.4% vs 3.1%; between-group difference, 10.3% [95% CI, 2.7% to 17.9%], P = .02).Conclusions and relevanceAmong patients with non-dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non-dialysis-dependent CKD.Trial registrationclinicaltrials.gov Identifier: NCT00946998.

Project description:BackgroundHome telemonitoring has developed considerably over recent years in chronic diseases in order to improve communication between healthcare professionals and patients and to promote early detection of deteriorating health status. In the nephrology setting, home telemonitoring has been evaluated in home dialysis patients but data are scarce concerning chronic kidney disease (CKD) patients before and after renal replacement therapy. The eNephro study is designed to assess the cost effectiveness, clinical/biological impact, and patient perception of a home telemonitoring for CKD patients. Our purpose is to present the rationale, design and organisational aspects of this study.MethodseNephro is a pragmatic randomised controlled trial, comparing home telemonitoring versus usual care in three populations of CKD patients: stage 3B/4 (n = 320); stage 5D CKD on dialysis (n = 260); stage 5 T CKD treated with transplantation (n= 260). Five hospitals and three not-for-profit providers managing self-care dialysis situated in three administrative regions in France are participating. The trial began in December 2015, with a scheduled 12-month inclusion period and 12 months follow-up. Outcomes include clinical and biological data (e.g. blood pressure, haemoglobin) collected from patient records, perceived health status (e.g. health related quality of life) collected from self-administered questionnaires, and health expenditure data retrieved from the French health insurance database (SNIIRAM) using a probabilistic matching procedure.DiscussionThe hypothesis is that home telemonitoring enables better control of clinical and biological parameters as well as improved perceived health status. This better control should limit emergency consultations and hospitalisations leading to decreased healthcare expenditure, compensating for the financial investment due to the telemedicine system.Trial registrationThis study has been registered at ClinicalTrials.gov under NCT02082093 (date of registration: February 14, 2014).

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Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST).

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Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST).

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