Randomized Trial Comparison of Ototoxicity Monitoring Programs

Study Overview
=================
Brief Summary
-----------------
This study involves research. Some chemotherapeutic drugs that can permanently reduce hearing are termed ototoxic. One such drug is the chemotherapy called cisplatin. Currently, if a patient is receiving cisplatin, hearing is tested in the Audiology Clinic using lengthy protocols and may be retested only when it is requested by their oncologist and when the Veteran can arrange an appointment. Researchers think that hearing testing prior to every treatment of cisplatin may reduce the number of Veterans who get disabling hearing loss from treatment. The purpose of this study is to compare the current method of monitoring hearing (audiology clinic protocols termed usual care) with a new portable hearing monitoring program (a comprehensive program of ototoxicity monitoring termed COMP-VA) that tests hearing using a portable hearing testing audiometer and a variety of efficient tools and techniques so that testing can occur prior to each cisplatin treatment at any quiet location in the hospital.

Detailed Description
-----------------
Research objectives are to compare the effectiveness of ototoxicity monitoring implemented using Comp-VA or usual care with regard to (1) improving Veterans' hearing and quality of life outcomes, (2) assisting oncologists in pre-treatment counseling and therapeutic planning and (3) increasing use of post-treatment rehabilitative services. The investigators plan to recruit a total of 320 Veterans undergoing cisplatin chemotherapeutic treatment over 4 years and 120 control subjects. Program Evaluation: Hearing testing prior to treatment will be done in order to establish eligibility, enroll and randomize each subject into one of two study arms. At 5 weeks and at one year post-randomization hearing will be re-tested in order to obtain an estimate of longitudinal trends in hearing and quality of life assessment. Use of audiological services following treatment from the randomized subjects will be tracked. Finally, data will also be collected at each treatment interval to track use of counseling tools and oncology personnel treatment decisions. Serial measurements from subjects receiving cisplatin prior to treatment who are randomized to: Comp-VA group will get a screening hearing test prior to treatment, at each treatment interval and at one-month post-treatment. Auditory testing will be done on or near the Chemo Unit and will include otoscopy, immittance testing, and a hearing testing done by the Veteran using a self-testing procedure, and may be tested using distortion product otoacoustic emissions (DPOAEs), if they cannot take a reliable hearing test. Usual care group will receive a full audiometric evaluation (otoscopy, immittance testing, air conduction and bone conduction hearing testing, speech audiometry, and distortion product otoacoustic emissions, DPOAEs) scheduled in the audiology clinic sound booth according to Audiology Service ototoxicity monitoring protocols. Testing will be arranged according to availability of appointments and patient convenience. Additionally data will also be collected from control subjects who are similar in age and are tested at intervals similar to the chemotherapy subjects.

Official Title
-----------------
Comprehensive Ototoxicity Monitoring Program for VA: A Randomized Trial

Conditions
-----------------
Cisplatin Ototoxicity, Hearing Loss

Intervention / Treatment
-----------------
* Other: COMP-VA
* Other: Standard of care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All Veterans entering cisplatin chemotherapy will be informed of the project and invited to participate unless the Veteran was excluded by CPRS review or medical advice. Exclusion Criteria: Experimental subjects must be prescribed cisplatin for treatment of cancer to be enrolled in the treatment arms of this study. Criteria for excluding subjects (chemotherapy and controls subjects) from this study will be: cognitively or physically unable to participate (patient or nurse report patient is incapable of participating), CPRS indication that subject exhibits aggressive behavior, subject has documented dementia, Alzheimer's disease, or severe psychosocial disorder, CPRS notes indicate individual is not legally capable of providing informed consent (subject has a legal guardian) unable to provide reliable behavioral hearing test responses (for either program evaluation hearing test or baseline, pre -treatment hearing test) as indicated by intra-session behavioral threshold reliability criterion of > +5 dB) exhibits Meniere's disease or retrocochlear disorder based on hearing test results, patient report or notes in CPRS exhibits active or recent history of middle ear disorder based on otoscopy, tympanometry, patient report, or notes in CPRS unwilling to participate hearing thresholds > 70 dB SPL at 4 kHz and below (based on DPOAE 'no response' data from a similar protocol described in Bibliography Reference 32, Table 3). The last exclusion was adopted in an effort to increase the potential that DPOAEs will be measurable in a large number of subjects.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COMP-VA<br>Hearing testing at each treatment and at 1 month following treatment. | Other: COMP-VA<br>* Hearing testing at each treatment interval by the comp-va audiologist<br>|
| Experimental: Usual Care<br>Hearing testing done according to Audiology Clinic protocol | Other: Standard of care<br>* Hearing testing done in the audiology clinic after oncology referral or patient self referral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Ototoxic Hearing Shift | Veterans randomized to the COMP-VA arm will have improved hearing outcomes (a) fewer ASHA-significant threshold shifts, (b) fewer CTCAE grade 1 or greater hearing shifts at Program Evaluation 3 as compared with Veterans randomized to the Usual Care arm. ASHA Shift is defined as: 20 dB shift at a single frequency 10 dB shift at two adjacent frequencies loss of response at three adjacent frequencies CTCAE Grade 1 or greater ototoxicity = hearing shift of 15-25 dB averaged at 2 contiguous test frequencies | 35 days post randomization | 
| Number of Participants Who Accessed the Audiology Clinic for Aural Rehabilitation | Veterans randomized to Comp-VA will access and use audiology rehabilitation at higher rates than usual care up to 1 year post-treatment. This includes: New hearing aid issued; Hearing aid adjustments made; Technology updated. | through study completion, an average of 1 year post randomization | 
| Number of Participants With Mortality | Mortality among participants defined as differences in rates of death within one year of randomization. | 1 year post randomization | 
| Hearing-related Quality of Life Measure | Differences in the Hearing Handicap Inventory for Adults (HHIA) questionnaire score [or Hearing Handicap Inventory for the Elderly (HHIE) score as appropriate] depending on the age of the subject. Minimum possible value = 0 Maximum possible value = 100 A higher score indicates poorer performance | 1 year post randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hearing, cisplatin, Ototoxicity, Veterans