Does Aspirin Have a Protective Role Against Chemotherapeutically Induced Ototoxicity?
NCT ID: NCT00578760
Last Updated: 2007-12-21
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
NA
110 participants
INTERVENTIONAL
2008-02-29
2010-02-28
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The researchers hypothesise that low-dose aspirin can prevent cisplatin induced ototoxicity in the clinical setting.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
42% of 400 patients receiving high-dose cisplatin (70-85 mg/m2, median cumulative dose 420mg) experienced common toxicity criteria (CTC: appendix 1) grade 3 or 4 symptoms (De Jongh 2003). Ototoxicity is dose related: 75-100% of patients receiving a very high dose and 20-40% with a low dose regime will develop significant ototoxic symptoms. In one study, 50% of head and neck cancer patients treated with cisplatin develop ototoxicity (Blakley 1994).
Cisplatin ototoxicity can present as a variable collection of symptoms and signs. These include bilateral and symmetrical hearing loss that is permanent and irreversible. High frequency sensorineural hearing loss with progression towards lower frequencies. Tinnitus, that is also permanent and irreversible.
There are a number of known factors that can predispose to cisplatin ototoxicity. They include: Dose, duration and mode of administration, age extremes, previous or concurrent cranial irradiation, previous history of hearing loss, renal disease, concomitant use of other ototoxic drugs, noise exposure with concomitant cisplatin administration, decreased serum albumin level, low hemoglobin level, low red blood cell count and a low haematocrit. Interestingly, cisplatin ototoxicity is considered to be exclusively confined to the cochlear, the vestibular system is unaffected (Myers 1993).
Ototoxicity from chemotherapeutic agents is due, in part, to reactive oxygen species. Reactive oxygen species can be attenuated by antioxidants. Salicylates are antioxidants that can be administered as aspirin.
It has been shown, in an animal model, that aspirin can protect hearing from cisplatin induced ototoxicity (Li 2002). In this set of experiments, the rat was used to evaluate the protective role of aspirin in both the acute and chronic setting. Auditory evoked brain stem responses were used to determine pre- and post-intervention hearing thresholds. In the acute experiments (n=23), one dose of cisplatin (16mg/kg) was administered and the animals were given aspirin (100mg/kg) starting the day before cisplatin treatment and continuing 4 days thereafter. There was a significant difference in hearing thresholds between the treatment and control groups at 3, 8 and 14kHz.
In the chronic experiments cisplatin was given on days 1, 4 and 7 (5mg/kg). Aspirin was given from 2 days before to 3 days after cisplatin treatment (100mg/kg bd). The hearing thresholds were compared before the first dose and 10 days after the last treatment. In those animals treated concurrently with aspirin, their hearing did not differ form control animals at 16 and 24 kHz. This was correlated to a significant reduction in inner hair cell loss from 20% (cisplatin) to 8% (cisplatin and aspirin).
Salicylates also protected renal function as determined by both plasma blood urea nitrogen and creatinine levels.
Salicylates did not affect tumour mass or metastasis. The rats were inoculated with malignant breast cancer cells (metastatic mammary adenocarcinoma). Aspirin protected against cisplatin-induced ototoxicity, without affecting the oncolytic action of the cisplatin.
Gentamicin and cisplatin both have a similar ototoxic mechanism of action. Aspirin has been shown to prevent gentamicin-induced hearing loss without compromising its anti-bacterial efficacy in both animal models and the clinical setting (Sha 2006, Chen 2007). Sha's group reported a prospective, randomized, double-blind trial with 200 patients. The patients all required gentamycin for clinical indications. In the 'treatment' arm of the study, the patients also received aspirin (1g tds for 14 days). A significant difference in hearing was shown at 6 and 8kHz of \>15dB if aspirin was not given.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
2
placebo OD during course of chemotherapy
placebo
OD for course of cisplatin chemotherapy
1
325mg ASA OD during course of chemotherapy
aspirin
325mg ASA OD for the duration of the cisplatin
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
aspirin
325mg ASA OD for the duration of the cisplatin
placebo
OD for course of cisplatin chemotherapy
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* germ-cell
* bladder
* head and neck (Only head and neck patients requiring only 2 cycles of post-operative chemo-radiotherapy, and therefore not requiring a gastrostomy tube, will be enrolled.)
* Over 18 years of age
* Normal otoscopic examination
* Informed consent
Exclusion Criteria
* Not able to grasp the study implications or unable to consent.
* History of peptic ulcer disease
* Severe renal impairment (U\&E, Cr clearance)
* Haemophilia
* Severe hepatic impairment
* Cerebrovascular haemorrhage
* Acute gout
* Hypersensitivity to NSAIDs
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University Health Network, Toronto
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
UNH
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Princess Margaret Hospital
Toronto, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Aspirin-01
Identifier Type: -
Identifier Source: org_study_id