Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000543189
Ethics application status
Approved
Date submitted
26/03/2019
Date registered
5/04/2019
Date last updated
2/12/2022
Date data sharing statement initially provided
5/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
IMPACT - Intervention to Manage PTSD And Comorbidities after Trauma Study
Scientific title
A randomised controlled trial to test the efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) compared to Prolonged Exposure (PE) for PTSD
Secondary ID [1] 296904 0
None
Universal Trial Number (UTN)
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Posttraumatic Stress Disorder (PTSD) 310858 0
Anxiety 311721 0
Depression 311722 0
Condition category
Condition code
Mental Health 309529 309529 0 0
Other mental health disorders
Mental Health 310349 310349 0 0
Anxiety
Mental Health 310698 310698 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The IMPACT trial is a non-inferiority Randomised Controlled Trial (RCT) that is comparing a non-trauma focussed transdiagnostic treatment known as the Unified Protocol (UP) (Barlow et al., 2017), to gold-standard Prolonged Exposure (PE) (Foa et al., 2007), for participants with PTSD. The UP therapy involves targeting shared features that are said to underlie emotional disorders such as cognitive distortions, emotional avoidance, maladaptive emotion driven behaviours, and emotional dysregulation. The manualised transdiagnostic UP treatment originally involved 10 weekly 90 minute face to face or telehealth sessions delivered to the individual by a trained clinician. The UP treatment will be delivered face-to-face at the Phoenix Traumatic Stress Research Clinic at the Royal Melbourne Hospital (Royal Park), via outreach (in participants home), or via telehealth using videoconferencing.
Intervention code [1] 313180 0
Treatment: Other
Comparator / control treatment
The active comparison condition is standard Prolonged Exposure (PE) (Foa et al., 2007). PE is a cognitive behavioural intervention that involves helping the person address and confront in a graduated way, traumatic memories and avoided situations in a supportive, controlled and safe environment, in order to reduce the associated fear and modify interpretations of the traumatic event that are impeding recovery. The manualised PE treatment involves 10 weekly 90-minute face-to-face sessions delivered to the individual by a trained clinician. The PE treatment will be delivered face-to-face at the Phoenix Traumatic Stress Research Clinic at the Royal Melbourne Hospital (Royal Park), via outreach (in participants home), or via telehealth using videoconferencing.
Control group
Active

Outcomes
Primary outcome [1] 308483 0
PTSD symptom severity as measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Timepoint [1] 308483 0
Pre-treatment (week prior to commencing treatment) , Post-treatment (2 weeks post-treatment)
Secondary outcome [1] 355124 0
PTSD symptom severity as measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).
Timepoint [1] 355124 0
6-month follow-up (6 months after T2)
Secondary outcome [2] 355126 0
PTSD caseness (i.e., diagnosis) as measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Timepoint [2] 355126 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [3] 367764 0
Severity of PTSD symptoms as measured by the PCL-5
Timepoint [3] 367764 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [4] 367765 0
Severity of anxiety as measured by the Generalised Anxiety Disorder Assessment-7 (GAD-7)
Timepoint [4] 367765 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [5] 367766 0
Severity of depression as measured by the Patient Health Questionnaire (PHQ-9)
Timepoint [5] 367766 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [6] 367767 0
Quality of life as measured by the Assessment of Quality of Life Questionnaire - 6D (AQoL-6D)
Timepoint [6] 367767 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [7] 367768 0
Alcohol use as measured by the Alcohol Use Disorders Identification Test (AUDIT)
Timepoint [7] 367768 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment), 6-month follow-up (6 months after post-treatment assessment)
Secondary outcome [8] 393139 0
Caseness of Complex PTSD (CPTSD) as measured by the International Trauma Questionnaire that has been included.
Timepoint [8] 393139 0
Pre-treatment (week prior to commencing treatment), post-treatment (2 weeks post-treatment, 6-month follow-up (6 months after post-treatment assessment)

Eligibility
Key inclusion criteria
(a) 18 years old and over
(b) Meeting diagnostic threshold for PTSD on the MINI 7 (PTSD module) after experiencing a traumatic event (at any time-point in their life)
(c) Provision of consent to partake in therapy
(d) English comprehension at a level to make informed consent
(e) If on psychotropic medication, on a stable dose for the last 4 weeks, and not intending to change for the duration of the treatment phase.
(f) For telehealth modality only: ability to reliably participate in telehealth treatment delivery, including appropriate technology for videoconferencing
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(a) Cognitive impairment
(b) Active mania or psychosis or suicidal ideation or other active risk
(c) Severe alcohol or substance use disorder
(d) Currently undergoing psychological treatment as assessed against a checklist of known psychological interventions.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will occur following the determination of eligibility by the study assessor, coordinated via the REDCap randomisation software by the project manager. Randomisation will be conducted according to a computer generated randomisation list provided by the blinded study statistician.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified randomisation will be used to improve the chance of balance among treatment groups, with respect to the following stratification variable: comorbidity (yes/no)

Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample Size Calculations:
Sample size has been determined for detecting non-inferiority of the CAPS score, where non-inferiority is declared if the upper endpoint of the 95% confidence interval for the difference in mean change scores is 10 CAPS-5 points from baseline to 6 months between UP and PE (adjusted for baseline). We will test a non-inferiority hypothesis that PTSD symptom severity outcomes in the UP condition will be non-inferior to those in PE. The non-inferiority margin – or the maximum amount by which UP can be worse than PE without having a clinical meaningful difference – was originally determined to be six points on the CAPS based on a single study CAPS-5 (Forbes et al., 2012). However, during the conduct of the study several non-inferiority PTSD studies were published that defined a clinical meaningful difference on the CAPS-5 as 10 points (Green et al., 2008; Litz et al., 2021; Morland et al., 2015; Nidich et al., 2018; Sloan et al., 2021; Sloan, et al., 2016) and in consultation with the Data Safety and Monitoring Board (DSMB), we adopted a 10-point non-inferiority margin (hence, the clinical trial registry was updated). A power calculation was conducted based on the primary study aim of testing non-inferiority based on the CAPS-5 PTSD symptom severity scores. A sample size of 100 was determined for detecting non-inferiority of the CAPS-5 score, where non-inferiority is declared if the upper endpoint of the 95% confidence interval for the difference in mean change scores from baseline to post-treatment between UP and PE (adjusted for baseline), is less than ten points on the CAPS-5. A total of 100 participants are required to detect non-inferiority with 80% power when UP is truly non-inferior. The false positive error rate (i.e., falsely declaring non-inferiority) with this design is at most 2.5%. Allowing for 20% loss to follow up pre/post study, the sample size increases to 120 patients.

Statistical analyses:
Data will be analysed in accordance with intention to treat (ITT) principles, using Multiple Imputation (MI) for missing data and with baseline and post-baseline auxiliary information included in the imputation model. Baseline characteristics of UP and PE conditions will be tabulated and analysed descriptively in the first instance. Non-inferiority analyses of the primary outcome at immediate post-treatment will then be performed using linear models adjusted for baseline outcome values and the stratification variable, and with treatment condition as the covariate of interest. Results will be presented as adjusted differences in change scores on the CAPS, comparing UP and PE, together with 95% confidence intervals. Non-inferiority of UP to PE will be accepted if the boundaries of a two-sided 95% CI are within the non-inferiority margin (which is a 10-point difference on the CAPS, with a standard deviation of 20.0). Supplementary ‘as treated’ and ‘per protocol’ analyses will also be performed to account for lack of treatment adherence. In addition to the non-inferiority analyses, standard linear and mixed effects models will be used to investigate the effects of time and group on the secondary outcome measures, while standardised within-group and between-group effect sizes will also be produced.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/04/2019
Actual
19/04/2019
Date of last participant enrolment
Anticipated
29/06/2023
Actual
Date of last data collection
Anticipated
31/03/2024
Actual
Sample size
Target
120
Accrual to date
102
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 301471 0
Government body
Name [1] 301471 0
National Health and Medical Research Council (NHMRC)
Country [1] 301471 0
Australia
Funding source category [2] 312787 0
Other Collaborative groups
Name [2] 312787 0
Atlas Institute for Veterans and Families
Country [2] 312787 0
Canada
Primary sponsor type
University
Name
Phoenix Australia, Centre for Posttraumatic Mental Health, Department of Psychiatry, University of Melbourne
Address
161 Barry Street, Carlton, VIC, Australia, 3053
Country
Australia
Secondary sponsor category [1] 301163 0
None
Name [1] 301163 0
Address [1] 301163 0
Country [1] 301163 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302216 0
University of Melbourne, Faculty of Medicine and Dentistry, Psychiatry Human Research Ethics Group (HEAG)
Ethics committee address [1] 302216 0
161 Barry Street,
Carlton, Victoria, 3053, Australia
Ethics committee country [1] 302216 0
Australia
Date submitted for ethics approval [1] 302216 0
29/10/2018
Approval date [1] 302216 0
22/02/2019
Ethics approval number [1] 302216 0
Ethics ID: 1853047.1

Summary
Brief summary
After exposure to a traumatic or stressful event, some people develop emotional disorders such as posttraumatic stress disorder (PTSD). Trauma-focussed psychological interventions, such as the gold standard Prolonged Exposure (PE) are empirically supported, first-line treatments for PTSD. However, non-response and drop-out rates are high with PE and many mental health clinicians do not use trauma-focussed treatments to treat PTSD. Using a randomised controlled trial design, this project aims to evaluate the efficacy of a non-trauma focussed transdiagnostic intervention called the Unified Protocol (UP) which targets features associated with PTSD including emotional dysregulation and cognitive distortions, compared to the gold-standard prolonged exposure (PE) therapy for the treatment of PTSD. Eligible participants will be randomly allocated to 10 weekly 90 minute sessions of UP or PE with pre-treatment, post-treatment and 6-month follow-up assessments. We hypothesise that UP and PE will be equally effective in treating PTSD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89478 0
Prof Meaghan O'Donnell
Address 89478 0
Phoenix Australia - Centre for Posttraumatic Mental Health
Level 3 Alan Gilbert Building
161 Barry Street
Carlton 3053
VIC
Australia
Country 89478 0
Australia
Phone 89478 0
+61 3 9035 7883
Fax 89478 0
Email 89478 0
[email protected]
Contact person for public queries
Name 89479 0
Dr Winnie Lau
Address 89479 0
Phoenix Australia - Centre for Posttraumatic Mental Health
Level 3 Alan Gilbert Building
161 Barry Street
Carlton 3053
VIC
Australia
Country 89479 0
Australia
Phone 89479 0
+61 39035 3593
Fax 89479 0
Email 89479 0
[email protected]
Contact person for scientific queries
Name 89480 0
Dr Winnie Lau
Address 89480 0
Phoenix Australia - Centre for Posttraumatic Mental Health
Level 3 Alan Gilbert Building
161 Barry Street
Carlton 3053
VIC
Australia
Country 89480 0
Australia
Phone 89480 0
+61 39035 3593
Fax 89480 0
Email 89480 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Results will be analysed at the treatment group data level, and any results from this trial that are published in scientific journals will publish group data only. Therefore individual, raw-line-by-line data will not be published for each participant.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseComparing the unified protocol for transdiagnostic treatment of emotional disorders to prolonged exposure for the treatment of PTSD: Design of a non-inferiority randomized controlled trial.2023https://dx.doi.org/10.1016/j.conctc.2023.101134
N.B. These documents automatically identified may not have been verified by the study sponsor.