Fahimi et al. (2011): Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens

Reference ↗
Title	Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens
Topic	Ginger
Author	Fahimi, F, Khodadad, K, Amini, S, Naghibi, F, Salamzadeh, J, Baniasadi, S
Year	2011
Journal	Iranian Journal of Pharmaceutical Research
DOI	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828901/

Brief summary

This study investigated the effect of ginger (Zingiber officinale) on nausea and vomiting in patients undergoing cisplatin-based chemotherapy. Patients were randomly divided into two groups: one group received ginger capsules (from the ginger root), and the other received a placebo in their first chemotherapy cycle. All patients additionally received standard medications to prevent chemotherapy-induced nausea and vomiting (CINV). In the next cycle, the groups were switched, so the ginger group received the placebo and vice versa. Among the 36 patients who completed both treatment cycles, there was no difference in the frequency, severity, or duration of acute and delayed nausea and vomiting. Adding ginger to the standard antiemetic medication showed no additional benefit for patients undergoing cisplatin-based chemotherapy in this study. This study provides little information on prior treatments or whether patients were comparable at the start. Additionally, there is no information on potential side effects of ginger or any conflicts of interest from the authors.

In dieser Studie wurde die Wirkung von Ingwer (Zingiber officinale) auf Übelkeit und Erbrechen bei Patienten unter Cisplatin-basierter Chemotherapie untersucht. Die Patienten wurden zufällig in zwei Gruppen aufgeteilt: Die eine Gruppe erhielt Ingwerkapseln (aus der Ingwerwurzel), die andere ein Placebo in ihrem ersten Chemotherapiezyklus. Alle Patienten erhielten zusätzlich Standard-Medikamente gegen die durch Chemotherapie verursachte Übelkeit und das Erbrechen (CINV). Im nächsten Zyklus wechselten die Gruppen, sodass die Ingwer-Gruppe das Placebo bekam und umgekehrt. Von den 36 Patienten, die beide Behandlungszyklen durchliefen, zeigte sich kein Unterschied in der Häufigkeit, Schwere oder Dauer von akuter und verzögerter Übelkeit und Erbrechen. Die Zugabe von Ingwer zum Standard-Medikament gegen Übelkeit und Erbrechen zeigte in dieser Studie keinen zusätzlichen Vorteil für Patienten mit Cisplatin-basierter Chemotherapie. Diese Studie gibt wenig Informationen über vorangegangene Therapien oder ob die Patienten zu Beginn vergleichbar waren. Zusätzlich werden keine Informationen zu eventuellen Nebenwirkungen von Ingwer oder Interessenskonflikten der Autoren angegeben.

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	Yes
Number of arms	2

Study characteristics

Inclusion criteria	Diagnosis of cancer and receiving cisplatin-based regimens at least for two cycles of the chemotherapy, receiveing one of the standard antiemetic regimens [5-HT3 antagonist (granisetrone) and corticostreoid (hydrocortisone)], being able to swallow capsules
Exclusion criteria	Clinical evidence of current or impending bowel obstruction, current radiotherapy, that is classified as high or intermediate risk of causing nausea and vomiting; pregnancy or lactation, concurrent use of ginger products
N randomized	50
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	McNemar and the Wilcoxon Signed Rank tests were used
Countries of data collection	Iran
LoE Level of evidence	Level 2 Oxford 2011
Outcome timeline Data collection times	T1: Day 1 T2: Day 2 T3: Day 3

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	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 chemotherapy regimens, n (%) Cisplatin + Etoposide 7 (19%) Cisplatin + Gemcitabine 7 (19%) Cisplatin + Docetaxel 11 (31%) Cisplatin + Vinorelbine 4 (11%) Cisplatin + Cyclophosphamide + Doxorubicin 4 (11%) Cisplatin + Paclitaxel + Doxorubicin 1 (3%) Cisplatin + 5-FU + Docetaxel 1 (3%) Cisplatin + Pemetrexed 1 (3%)
Previous cancer therapies	NI
Gender	Mixed
Gender specifications	28 % female
Age groups	Adults (18+)
Age groups specification	Mean(SD): 50.53 (12.21) 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	-999
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Not seperated by arm, n=14 overall
Drop-out reasons	Not seperated by arm, overall: due to lack of compliance, n=1 due to pruritus and gastrointestinal complaints
Intervention	Ginger capsules
Dosage and regime	Four capsules of powdered ginger (Zintoma®, Gol Daru) daily (each capsule contained 250 mg of ginger)
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.	3
Side effects / Interactions	NI

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	-999
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Not seperated by arm, n=14 overall
Drop-out reasons	Not seperated by arm, overall: due to lack of compliance, n=1 due to pruritus and gastrointestinal complaints
Intervention	Placebo
Dosage and regime	Four capsules of placebo (lactose)
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.	3
Side effects / Interactions	NI

Outcomes

Nausea

Outcome type As specificed by the authors	Primary
Outcome specification	Prevalence, severity and duration of nausea in acute (day 1) and delayed phases (day 2-3)
Type of measurement	Observation
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".	Prevalence intervention vs. placebo: acute (day 1) 47% vs. 58%, p=0.388, ns. delayed day 2: 44.5% vs. 53%, p=0.508, ns. delayed day 3: 47% vs. 50%, p<0.999, ns. Severity (Mean(SD)) intervention vs. placebo: acute (day 1): 1.75(2.02) vs. 1.36(1.91), p=0.14, ns. delayed day 2: 1.78(1.93) vs. 1.5(2.03), p=0.31, ns. delayed day 3: 1.61(1.93) vs. 1.47(1.92), p=0.73, ns. Duration (Mean(SD)) intervention vs. placebo in h: acute (day 1): 2.18(5.03) vs. 2.27(4.88), p=0.93, ns. delayed day 2: 3.06(7.61) vs. 5.10(9.66), p=0.59, ns. delayed day 3: 2.67(6.76) vs. 3.80(8.55), p=0.82, ns.

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	some concerns
Bias due to deviation from intended intervention (assignment to intervention)	some concerns
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	some concerns
Bias in measurement of the outcome	some concerns
Bias in selection of the reported result	some concerns
Other sources of bias	some concerns
Overall RoB judgment	some concerns

Vomiting

Outcome type As specificed by the authors	Secondary
Outcome specification	Prevalence and severity of vomiting in acute (day 1) and delayed phases (day 2-3)
Type of measurement	Observation
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".	Prevalence intervention vs. placebo: acute (day 1): 58% vs. 75%, p=0.070, ns. delayed day 2: 75% vs. 81%, p=0.687, ns. delayed day 3: 81% vs. 78%, p<0.999, ns. Severity (Mean(SD)): acute (day 1): 1.47(2.18) vs. 0.94(1.77), p=0.14, ns. delayed day 2: 1.03(1.89) vs. 0.83(1.84), p=0.72, ns. delayed day 3: 0.80(1.83) vs. 0.92(1.86), p=0.78, ns.

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	some concerns
Bias due to deviation from intended intervention (assignment to intervention)	some concerns
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	some concerns
Bias in measurement of the outcome	some concerns
Bias in selection of the reported result	some concerns
Other sources of bias	some concerns
Overall RoB judgment	some concerns

Funding and Conflicts of Interest

Funding	NI
Conflicts of Interest	NI

Further points for assessing the study

Sample

Power analysis performed	NI
- Sample size corresponds to power analysis	NA
- Reasons for insufficient sample size based on power analysis	Sample size based on a similar study
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	No
Ethnicity mentioned	No

Alternative Explanation

Other explanations for an effect besides the investigated intervention	No
- Possibility of attention effects	NA
- Possibility of placebo effects	NA
- Other reasons	NA

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	Yes
Correction for multiple testing	NA
Measurement of compliance	No
Consistent reporting in numbers (figures, flowchart, abstract, results)	Yes
Comprehensive and coherent reporting	No
Cross-over	Yes
- Sufficient washout period	Yes
- Tested for carry-over effects	No
- Tested for sequence effects	No

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	No
Side effects systematically recorded	NI
Side effects considered in result interpretation	NA
Ethics votum	Yes