Panahi et al. (2012): Effect of Ginger on Acute and Delayed Chemotherapy-Induced Nausea and Vomiting: A Pilot, Randomized, Open-Label Clinical Trial

Reference ↗
Title	Effect of Ginger on Acute and Delayed Chemotherapy-Induced Nausea and Vomiting: A Pilot, Randomized, Open-Label Clinical Trial
Topic	Ginger
Author	Panahi, Y, Saadat, A, Sahebkar, A, Hashemian, F, Taghikhani, M, Abolhasani, E
Year	2012
Journal	Integrative Cancer Therapies
DOI	https://doi.org/10.1177/15347354114332

Brief summary

In this open-label pilot study, 100 women with advanced breast cancer participated, all receiving standard chemotherapy with docetaxel, epirubicin, and cyclophosphamide. They were randomly divided into two groups: one group received ginger (1.5 g/day in 3 doses every 8 hours) in addition to the standard antiemetic therapy (granisetron plus dexamethasone), while the other group received only the standard therapy (control group). Ginger was taken for 4 days, starting with the onset of chemotherapy. The frequency, extent, and severity of nausea, vomiting, and retching were measured. Results showed that the frequency of nausea was significantly lower in the ginger group 6 to 24 hours after chemotherapy. Beyond this period, however, ginger provided no additional benefit in reducing the frequency or severity of nausea, vomiting, and retching in other assessed timeframes. The study’s open-label design means that participants knew their group assignment, which could influence their self-reported assessments, introducing potential bias. Additionally, group assignment was based on alternating days, which cannot be considered fully random. A key issue is the lack of baseline characteristic data. Although the authors state that the groups were comparable at the beginning of the study, this cannot be verified.

In dieser offenen Pilotstudie nahmen 100 Frauen mit fortgeschrittenem Brustkrebs teil, die eine Standard-Chemotherapie mit Docetaxel, Epirubicin und Cyclophosphamid erhielten. Sie wurden zufällig in zwei Gruppen eingeteilt: Eine Gruppe erhielt zusätzlich zur Standardtherapie gegen Übelkeit (Granisetron plus Dexamethason) Ingwer (1,5 g/Tag in 3 Dosen alle 8 Stunden), die andere nur die Standardtherapie (Kontrollgruppe). Die Einnahme von Ingwer dauerte 4 Tage, beginnend mit dem Start der Chemotherapie. Gemessen wurde die Häufigkeit, das Ausmaß und die Schwere von Übelkeit, Erbrechen und Würgen. Die Ergebnisse zeigen, dass die Häufigkeit von Übelkeit in der Ingwer-Gruppe in den 6 bis 24 Stunden nach der Chemotherapie bedeutsam niedriger war. Abgesehen davon zeigte Ingwer jedoch keinen zusätzlichen Nutzen zur Reduzierung der Häufigkeit oder Schwere von Übelkeit, Erbrechen und Würgen in den anderen untersuchten Zeiträumen. Die Studie hat ein offenes Design, bedeutet die Teilnehmer wussten ihre Gruppenzuteilung, was zur Verzerrung der eigenen Einschätzung führen kann. Zusätzlich wurde die Gruppenzuteilung über wechselnde Tage verwirklicht, was nicht als nicht völlig zufällig betrachtet werden kann. Besonders problematisch ist jedoch, dass es keine Angaben von Baseline Charakteristika gibt. Auch wenn die Gruppen laut Autoren zu Beginn der Studie vergleichbar waren, kann dies nicht überprüft werden.

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	No
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	Women who had cancer (mainly new cases of advanced breast cancer diagnosed by the oncologist and thus undergoing their first experience of chemotherapy) who were initially assigned to the components of TEC regimen, including docetaxel, epirubicin, and cyclophosphamide
Exclusion criteria	Participation in another study with different drugs; history of bone marrow or stem cell transplantation; presence of respiratory, cardiovascular, liver, renal, metabolic, or gastrointestinal diseases; and history of motion sickness
N randomized	100
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.	PP Analysis
Specifications on analyses	Between-arm (ginger vs control) comparisons were performed using independent-samples t test (for quantitative variables) or χ2 and Fisher’s exact test (for categorical variables)
Countries of data collection	Iran
LoE Level of evidence	Level 2 Oxford 2011
Outcome timeline Data collection times	T1: 0-6h after Chemotherapy T2: 6-24h after Chemotherapy T3: 2nd day T4: 3rd day T5: 4th day

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.	Curative
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Breast Cancer, Other Cancers
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	Advanced Stage, NI
Specifications on cancer stages	Mainly new cases of advanced breast cancer diagnosed by the oncologist
Comorbidities	NI
Current cancer therapies	Chemotherapy
Specifications on cancer therapies	Patients experiencing their first trial of chemotherapy (Docetaxel, Epirubicin, Cyclophosphamid)
Previous cancer therapies	No therapy
Gender	Female
Gender specifications	100 % female
Age groups	Adults (18+)
Age groups specification	Age range = 35-74 years, mean(SD) = 51.83(9.18) 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	50
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	13
Drop-out reasons	Lost to follow-up or lack of compliance
Intervention	Ginger capsules (dried ginger powder) + all antiemetic standardtherapy (Granisetron + Dexamethason)
Dosage and regime	Daily dose 3x0.5g Every 8h, starting 30min after chemotherapy
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.	4
Side effects / Interactions	Heartburn, headache, vertigo

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	50
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	9
Drop-out reasons	Lost to follow-up or lack of compliance
Intervention	Placebo + all antiemetic standardtherapy (Granisetron + Dexamethason)
Dosage and regime	Every 8h, starting 30min after Chemotherapy
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.	4
Side effects / Interactions	NI

Outcomes

Nausea and Vomiting

Outcome type As specificed by the authors	Primary
Outcome specification	Prevalence of nausea, vomiting and retching
Type of measurement	Diary questionnaire
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".	Prevalence of nausea intervention vs. placebo: first 6 hours after chemotherapy: 24.3% vs. 41.5% (p=0.11, ns.) 6-24h after chemotherapy: 35.1% vs. 58.5% (p=0.04, sign.) second day: 45.9% vs. 55.0% (p=0.43, ns.) third day: 54.0% vs. 55.0% (p=0.93, ns.) fourth day: 56.8% vs. 47.5% (p=0.42) Prevalence of vomiting and retching intervention vs. placebo: first 6 hours after chemotherapy: 24.3% vs. 26.8% (p=0.80, ns.) 6-24h after chemotherapy: 18.9% vs. 29.8% (p=0.26, ns.) second day: 35.1% vs. 27.5% (p=0.47, ns.) third day: 35.1% vs. 30.0% (p=0.63, ns.) fourth day: 43.2% vs. 35.0% (p=0.46, ns.)
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".	NA

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	?

Nausea and Vomiting

Outcome type As specificed by the authors	Secondary
Outcome specification	Severity (Rhodes Index Scores) of Nausea, Vomiting, and Retching
Type of measurement	Diary questionnaire
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".	Intervention vs. placebo (Min, Mean(SD), Max): first 6h after chemotherapy: 0, 3.22(4.45), 15 vs. 0, 2.98 ± 3.95, 13 (p=0.80, ns.) 6-24h after chemotherapy: 0, 3.11(4.04), 16 vs. 0, 4.10(4.42), 17 (p=0.31, ns.) second day: 0, 4. 35(4.84), 19 vs. 0, 4.32(4.36), 14 (p=0.98, ns.) third day: 0, 4.78(4.82), 16 vs. 0, 4.22(5.06), 20 (p=0.62, ns.) fourth day: 0, 5.70(5.60), 23 vs. 0, 4.47(5.45), 2 (p=0.33, ns.)
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".	NA

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	?

Nausea and Vomiting

Outcome type As specificed by the authors	Secondary
Outcome specification	Proportion of participants with none, mild, moderate, or severe symptoms of nausea, vomiting, and retching
Type of measurement	Diary questionnaire
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".	Symptom severity intervention vs. placebo: first 6h after chemotherapy: none: 48.6% vs. 53.7% (p=0.66), mild: 32.4% vs. 31.7% (p=0.94), moderate: 18.9% vs. 14.6% (p=0.61), severe: 0% vs. 0% (p=1.00, ns.) 6-24h after chemotherapy: none: 45. 9% vs. 34.1% (p=0.29), mild: 40.5% vs. 46.13% (p=0.61), moderate: 13.5% vs. 17.1% (p=0.66), severe: 0% vs. 0% (p=1.00, ns.) second day: none: 40.5% vs. 35.0% (p=0.62), mild: 35.1% vs. 45. 0% (p=0.38), moderate: 21.6% vs. 20.0% (p=0.86), severe: 2.7% vs. 0% (p=0.48, ns.) third day: none: 37.8% vs. 35.0% (p=0.80), mild: 37.8% vs. 42.5% (p=0.68), moderate: 21.6% vs. 20.0% (p=0. 86), severe: 2.7% vs. 2.5% (p=1.00, ns.) fourth day: none: 32.4% vs. 45.0% (p=0.26), mild: 32.4% vs. 27.5% (p=0.64), moderate: 32.4% vs. 25.0% (p=0.47), severe: 2.7% vs. 2.5% (p=1.00, ns.)
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".	NA

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	This work was financially supported by the Baqiyatallah University of Medical Sciences.
Conflicts of Interest	The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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	sv
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	?