Clinical Trial Results:
A Pilot Randomised Controlled Trial of Drug Treatment for Depression in Patients undergoing Haemodialysis
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Summary
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EudraCT number |
2012-000547-27 |
Trial protocol |
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Global end of trial date |
13 Oct 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2019
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First version publication date |
29 Mar 2019
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Other versions |
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Summary report(s) |
EudraCT 2012-000547-27 Summary of results |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CTIMPMCRENAL12
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Additional study identifiers
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ISRCTN number |
ISRCTN06146268 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
ASSERTID: RD2012-37 | ||
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Sponsors
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Sponsor organisation name |
The University of Hertfordshire
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Sponsor organisation address |
College Lane, Hatfield, United Kingdom, AL10 9AB
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Public contact |
Dr Karin Friedli, University of Hertfordshire, 01707 286472, k.friedli1@herts.ac.uk
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Scientific contact |
Dr Karin Friedli, University of Hertfordshire, 01707 286472, k.friedli1@herts.ac.uk
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Sponsor organisation name |
East and North Hertfordshire NHS Trust
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Sponsor organisation address |
Coreys Mill Lane, Stevenage, United Kingdom, SG14AB
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Public contact |
Professor Phillip Smith, East and North Hertfordshire NHS Trust, 0203 826 2075, phillip.smith5@nhs.net
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Scientific contact |
Professor Ken Farrington, East and North Hertfordshire NHS Trust, 01438 284346, ken.farrington@nhs.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Oct 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Oct 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main research question is to evaluate the feasibility of conducting a randomised, double blind, placebo pilot trial in patients with end stage renal disease (ESRD) and depression. The treatment under investigation is Sertraline, a licensed anti-depressant. The study is split into four phases. Phase one will evaluate the number of ESRD patients eligible for this clinical trial. Phase two will assess the feasibility of conducting a randomised drug trial in this group of patients, by measuring the number who take part. Phase three will look at the safety and drug exposure of Sertraline in ESRD patients and phase four will explore the patient experience of participating in this trial.
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Protection of trial subjects |
Patients were afforded the opportunity to talk to a psychiatrist and were monitored carefully and frequently for their low mood.
Research staff conducted close monitoring of patients for serious adverse events/reactions of study IMP, particularly for signs of worsening depression and suicide ideation.
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Background therapy |
N/A | ||
Evidence for comparator |
Intervention: Sertraline hydrochloride, starting with 50 mgs orally per day for 2 months, with the option of stepping up to 100 orally mgs for remainder of the trial, if clinically indicated. Control: matched placebo. | ||
Actual start date of recruitment |
01 Aug 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
19
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
In total, 709 patients were screened and enrolled between April of 2013 and October of 2014. 37 were diagnosed with major depressive disorder, and 30 were randomised (15 patients to the intervention arm, 15 patients to the control arm) | |||||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion: 1. Patients with ESRD and receiving HD. They will have started dialysis at least 3 months ago and have continued to receive dialysis in the past 3 months prior to the invitation to take part in this study. 2. Adults aged 18 or over. 3. Patients who speak and read English sufficiently well to complete questionnaires. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||||||||
Blinding implementation details |
The study randomisation codes were only to be broken for medical and safety reasons. In addition blinding could be broken if:
1. requested by the Data Monitoring and Ethics Committee
2. a patient in the study is withdrawn due to the offer of a transplant
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention arm | |||||||||||||||||||||
Arm description |
Sertraline hydrochloride, starting with 50 mgs orally per day for 2 months, with the option of stepping up to 100 orally mgs for remainder of the trial | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Sertraline hydrochloride
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Investigational medicinal product code |
MIA(IMP)11149
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
50 mgs orally per day for 2 months, with the option of stepping up to 100 orally mgs for remainder of the trial
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Arm title
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Control arm | |||||||||||||||||||||
Arm description |
Control: matched placebo | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Matched Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
50mg orally once a day for one month
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
n/a
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Randomised patients
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End points reporting groups
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Reporting group title |
Intervention arm
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Reporting group description |
Sertraline hydrochloride, starting with 50 mgs orally per day for 2 months, with the option of stepping up to 100 orally mgs for remainder of the trial | ||
Reporting group title |
Control arm
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Reporting group description |
Control: matched placebo | ||
Subject analysis set title |
n/a
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Randomised patients
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End point title |
Primary [1] | |||||||||
End point description |
The primary aim was to assess the feasibility of undertaking a large RCT to evaluate the acceptability and effectiveness of sertraline to treat depression in patients on hemodialysis.
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End point type |
Primary
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End point timeframe |
from first patient first visit to last patient last visit.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Detailed statistical analyses available in attached publication. |
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Attachments |
Results summary |
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End point title |
Secondary endpoints | |||||||||
End point description |
Secondary outcomes included the number of patients not meeting the eligibility criteria, the number who refused to take part in the trial, the number who withdrew from the trial, the reasons given, and the number and nature of adverse events reported. Changes in MADRS and BDI-II scores over the course of the study were also evaluated. To estimate medication adherence, we also analysed information on the number of returned tablets and pre-and post-dialysis sertraline levels.
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End point type |
Secondary
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End point timeframe |
Duration of the trial
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Adverse events information
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Timeframe for reporting adverse events |
6 months following randomisation
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Adverse event reporting additional description |
Patients were reassessed by the psychiatrist at 2 weeks and 2, 4, and 6 months and assessed monthly by the research nurse.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MADRS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
n/a
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Reporting groups
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Reporting group title |
All randomised patients
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Reporting group description |
Intervention arm = 15 patients, control arm = 15 patients. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Jul 2013 |
Substantial Amendment 2 contained a number of protocol (V4.0) changes including the addition of two questionnaires, the Multidimensional Fatigue Inventory (MFI) and Short Form 36 (SF36) energy/fatigue subscale. These questionnaires were used to estimate the prevalence of fatigue and tiredness in ESRD patients as it is believed that Identification and management of fatigue improves the quality of life and might prevent patient from becoming depressed. Patients to be assessed for fatigue as well as depression, QoL, demographic and clinical measures during the prevalence and screening phase of the trial as well as at baseline, during and at the end of the trial. The protocol (V4.0) was changed so that in some trusts patients may initially be approached by letter with the PIS and a short version of the PIS attached. Once the patient has received this information, the research nurse to approach the patients in the same way as the other recruiting trusts. In protocol V4.0 it was assumed that all patients randomised to Arm A received Sertraline hydrochloride and arm B received placebo. This is not the case. In protocol V5.0 Patients to be randomised to Sertraline hydrochloride (Arm A or B) or a placebo (Arm A or B). The way in which SAE’s are reported was modified. In protocol V5.0 the CI, PIs or their deputies to complete the sponsor’s SAE form on the electronic CRF within 24 hours of his/her becoming aware of the event instead of completing a paper SAE form. The PI to produce a full written report within 5 days once the SAE has been fully managed and send it to the CI and the sponsors (as per GCP guidelines). Minor protocol changes were also made including the addition of new members to the study team at East and North Herts NHS Trust, the alteration of contact details and minor grammatical changes. The ASSERTID drug label (V5.0) was modified to reflect protocol changes. |
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09 Jan 2014 |
Key changes included: amendment objectives were amended to explore views of eligible patients on their willingness to enter a treatment trial, regardless of whether they had consented to take part or not. Inclusion criteria and study procedures were amended to explore reasons why patients choose to enter the trial or not be interviewing eligible patients who have declined to take part in the trial. The sample size estimation was amended in-line with recruitment rates. Patients were invited to take part in phase 2 regardless of whether they had originally consented to take part. An additional site and PI were added. |
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23 Apr 2015 |
Collection of additional data from the patients to estimate impact on depression and survival of patients in this high risk cohort.
Added C-Reactive Protein (CRP) as another data variable to collect at screening and at the nurse baseline assessment.
The archiving section was clarified in the protocol. A study guidance document was produced. New study document: AssertID Trial Patient Study Card
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Small sample size : RCT recruitment was difficult and constrained by exclusion of a high number of patients, a large proportion of whom were already receiving treatment for depression, and reluctance of chronically ill patients to participate. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/28126706 |
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