Study Note
Brief summary
Cisplatin is an effective chemotherapeutic agent. However, cisplatin is toxic to the outer hair cells of the ears and can cause hearing loss in patients receiving this therapy. In this study, the researchers tested the effect of Ginkgo biloba extract at a dose of 120 mg twice daily to prevent damage to the outer hair cells in patients receiving cisplatin. Patients receiving the placebo showed frequent damage to the hair cells over 90 days, taking Ginkgo reduced this damage in this small sample of patients studied. There were also no side effects of taking Ginkgo biloba extract in these patients.
Cisplatin ist ein effektives Chemotherapeutikum. Cisplatin ist jedoch giftig für die äußeren Haarzellen der Ohren und kann bei Patienten, die diese Therapie erhalten, einen Hörverlust verursachen. In dieser Studie testeten die Forscher die Wirkung von Ginkgo biloba-Extrakt in einer Dosis von 120 mg zweimal täglich, um Schäden an den äußeren Haarzellen bei Patienten, die Cisplatin erhielten, vorzubeugen. Patienten, die das Placebo erhielten, zeigten über 90 Tage lang häufig Schädigungen der Haarzellen, die Einnahme von Ginkgo verringerte diesen Schaden in dieser kleinen Stichprobe von untersuchten Patienten. Es gab auch keine Nebenwirkungen der Einnahme von Ginkgo biloba-Extrakt bei diesen Patienten.
Study Design
| Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies
|
Prospective
|
| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
|
Monocentric
|
| Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties
|
Double
|
| Is randomized
|
Yes
|
| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
|
No
|
| Number of arms
|
2
|
Study characteristics
| Inclusion criteria
|
Cancer patients, age ≥ 18 years, chemotherapy with cisplatin
|
| Exclusion criteria
|
History of middle or inner ear disease; prior therapy with cisplatin; abnormal audiometric and audiometric impedance tests and abnormal distortion product otoacoustic emissions (DOPOAEs) within the range of frequencies tested
|
| N randomized
|
15
|
| Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.
|
ITT Analysis
|
| Specifications on analyses
|
ITT not specified, but no drop-out reported.
|
| Countries of data collection
|
Brazil
|
| LoE Level of evidence
|
2b Oxford 2009
|
| Outcome timeline Data collection times
|
NI
|
Characteristics of participants
| Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.
|
NI
|
| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
|
NI
|
| Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis
|
NI
|
| Specifications on cancer stages
|
NI
|
| Comorbidities
|
NI
|
| Current cancer therapies
|
Chemotherapy
|
| Specifications on cancer therapies
|
Cisplatin
|
| Previous cancer therapies
|
NI
|
| Gender
|
NI
|
| Gender specifications
|
NI
|
| Age groups
|
Adults (18+)
|
| Age groups specification
|
Range 24–69 years
|
Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
|
Intervention
|
| Number of participants (arm) N randomized
|
8
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
0
|
| Drop-out reasons
|
NA
|
| Intervention
|
Ginkgo biloba extract 761
|
| Dosage and regime
|
Capsules, 120 mg 2x/day
Duration: throughout cisplatin therapy according to the respective protocol for the tumor (cumulative doses ranged from 50 to 300mg/m2).
|
| One-time application
|
No
|
| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.
|
-999
|
| Side effects / Interactions
|
No side effects in either arm.
No indications from the patient files that ginkgo influenced the anti-tumor effect of cisplatin.
|
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
|
Placebo
|
| Number of participants (arm) N randomized
|
7
|
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
|
0
|
| Drop-out reasons
|
NA
|
| Intervention
|
Placebo
|
| Dosage and regime
|
Capsules, 120 mg 2x/day
Duration: throughout cisplatin therapy according to the respective protocol for the tumor (cumulative doses ranged from 50 to 300mg/m2).
|
| One-time application
|
No
|
| Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.
|
-999
|
| Side effects / Interactions
|
No side effects in either arm.
No indications from the patient files that ginkgo influenced the anti-tumor effect of cisplatin.
|
Outcomes
Ototoxicity
| Outcome type As specificed by the authors
|
Primary
|
| Outcome specification
|
Distortion product otoacoustic emissions (DPOAEs), average of the amplitude of the signal and signal-noise (S/N) ratio (SNR)
Tested with Scout biologic equipment from bio-logic systems®
|
| Type of measurement
|
Otoacoustic Emissions Testing
|
| Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
NA
|
| Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".
|
Overall:
Significantly lower DPOAEs in placebo arm compared to ginkgo arm at a frequency of 8KHz, p=0.03
Significantly lower SNRs in placebo arm compared to Ginkgo arm at a frequency of 8KHz, p=0.04
|
| Risk of Bias Assessment: Cochrane RoB tool 2.0
|
| Bias arising from the randomization process
|
?
|
| Bias due to deviation from intended intervention (assignment to intervention)
|
?
|
| Bias due to deviation from intended intervention (adhering to intervention)
|
NA
|
| Bias due to missing outcome data
|
?
|
| Bias in measurement of the outcome
|
?
|
| Bias in selection of the reported result
|
?
|
| Other sources of bias
|
?
|
| Overall RoB judgment
|
?
|
Funding and Conflicts of Interest
| Funding
|
NI
|
| Conflicts of Interest
|
Verum was donated to the RCT.
|
Further points for assessing the study
Sample
| Power analysis performed
|
?
|
| - Sample size corresponds to power analysis
|
?
|
| - Reasons for insufficient sample size based on power analysis
|
?
|
| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
|
?
|
| Ethnicity mentioned
|
?
|
Alternative Explanation
| Other explanations for an effect besides the investigated intervention
|
?
|
| - Possibility of attention effects
|
?
|
| - Possibility of placebo effects
|
?
|
| - Other reasons
|
?
|
Statistics
| Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing
|
?
|
| Correction for multiple testing
|
?
|
| Measurement of compliance
|
?
|
| Consistent reporting in numbers (figures, flowchart, abstract, results)
|
?
|
| Comprehensive and coherent reporting
|
?
|
| Cross-over
|
?
|
| - Sufficient washout period
|
?
|
| - Tested for carry-over effects
|
?
|
| - Tested for sequence effects
|
?
|
Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
?
|
| Side effects systematically recorded
|
?
|
| Side effects considered in result interpretation
|
?
|
| Ethics votum
|
?
|
Additional Notes
CONTRA:
