Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000416493
Ethics application status
Approved
Date submitted
12/03/2016
Date registered
31/03/2016
Date last updated
28/02/2022
Date data sharing statement initially provided
19/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the efficacy, safety, and cost-effectiveness of adjuvant ginger supplementation for chemotherapy-induced nausea and vomiting
Scientific title
Supplemental Prophylactic Intervention for Chemotherapy induced nausea and Emesis (SPICE) trial of the efficacy, safety, and cost-effectiveness of adjuvant ginger supplementation: A multi-center randomized controlled trial
Secondary ID [1] 288751 0
none
Universal Trial Number (UTN)
Trial acronym
SPICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy-induced nausea 297995 0
Malnutrition 297996 0
Treatment-related fatigue 297997 0
Chemotherapy-induced vomiting 308799 0
Condition category
Condition code
Cancer 298151 298151 0 0
Any cancer
Alternative and Complementary Medicine 298310 298310 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1.2g standardised non-synthetic Ginger (Zingiber officinale) extract in capsule form; over-encapsulated with a non-gelatin capsule for blinding. Frequency: 4x300mg capsules (1.2g total) per day, every 3-5 hours with food. The ginger is standardised to contain 5% gingerols (15mg active ingredient per capsule; 60mg gingerols in total). Duration: 5 days per chemotherapy cycle (Day of chemotherapy and 4 days directly after) for three 3 cycles. Initial dose is 1 hour before chemotherapy commences. All participants will be provided the supplement or placebo in identical glass bottles of 60 capsules with a single desiccant for use throughout the entire treatment period. The usual diet is unmodified, although participants will be advised to consume no fresh ginger or ginger-containing products.
Intervention code [1] 294187 0
Treatment: Other
Comparator / control treatment
The placebo capsules given to the control group contain 150 - 200mg of the inner filler microcrystalline cellulose in a non-gelatin capsule, and will be prescribed the same dosing regimen as the intervention group.
Control group
Placebo

Outcomes
Primary outcome [1] 297661 0
chemotherapy-induced nausea related-quality of life as assessed by the FLIE-5DR self-reported questionnaire
Timepoint [1] 297661 0
Baseline and 5 days post chemotherapy for three chemotherapy cycles
Secondary outcome [1] 321734 0
Control of nausea and vomiting using the MAT self-reported questionnaire
Timepoint [1] 321734 0
End of the Day-1 and Day-5 of the first three chemotherapy cycles
Secondary outcome [2] 321735 0
Treatment-related fatigue as assessed using as assessed by the FACIT-F self-reported questionnaire
Timepoint [2] 321735 0
Baseline and 5 days post chemotherapy during each of the three chemotherapy cycles
Secondary outcome [3] 321736 0
Nutrition status as assessed using the PG-SGA assessment tool
Timepoint [3] 321736 0
At the commencement of first three chemotherapy cycles
Secondary outcome [4] 321737 0
Direct health-related costs (including all participant reported purchase of health-related product/services, hospital dietitian costs, standardised costs of any hospital admissions)
Timepoint [4] 321737 0
Data collected throughout study and assessed once trial period is complete
Secondary outcome [5] 322242 0
Adverse events as assessed using the National Cancer Institute Common Terminology Criteria for adverse events. These include patient-reported adverse events, platelet-related events (e.g. bruising, bleeding), and gastrointestinal symptoms (e.g.heartburn).
Timepoint [5] 322242 0
All adverse events will be reported from baseline to final study-related procedure (24 weeks)
Secondary outcome [6] 349340 0
Anticipatory nausea and vomiting (assessment tool designed by the researchers modelled on the Multinational Association of Supportive in Cancer Anti-emesis [MAT] tool)
Timepoint [6] 349340 0
Day before chemotherapy for the first 3 cycles.
Secondary outcome [7] 349341 0
Anxiety and depression measured by the Hospital Anxiety and Depression Scale (HADS) tool
Timepoint [7] 349341 0
Day 1 of the first three chemotherapy cycles
Secondary outcome [8] 349342 0
Health service use (participant's private purchase of health-related products and services, hospital dietitian service use, hospitalisations)
Timepoint [8] 349342 0
Day-5 of the 3rd cycle of chemotherapy or earlier if less than 3 cycles.
Secondary outcome [9] 349343 0
Global quality of life measured by the EQ-5D-5L
Timepoint [9] 349343 0
Day before chemotherapy and Day-5 of the first three chemotherapy cycles

Eligibility
Key inclusion criteria
• Chemotherapy-naive patients (no prior history of chemotherapy).
• Scheduled for chemotherapy classed as moderately or severely emetogenic. Moderate to highly emetogenic chemotherapy regimens informed by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) guideline from the Perugia consensus conference
• Scheduled for single or combined agent single-day chemotherapy regimen repeated in two, three or four-week cycles. Includes regimens with more than one type of chemotherapy agent delivered in single day doses equal to or greater than 7 days apart (e.g. as with AC-T regimens used in the treatment of breast cancer whereby cyclophosphamide and doxorubicin are administered on day one of the treatment cycle and paclitaxel is administered on days one, eight and fifteen of a 21-day cycle).
• Aged >18 years.
• Adequate physical function: baseline Karnofsky score > 60.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Concurrent radiotherapy.
• Non-English speaking persons.
• People with severe cognitive impairment preventing their ability to fully understand the purpose of the study, adhere to the intervention and complete data collection forms.
• Pregnant or lactating women.
• Concurrent use of other ginger-containing supplements and ingestion of any amount of fresh or dried ginger from 24 hours prior to chemotherapy to 7-days post chemotherapy (Cycle 1-3). Patients who plan to consume ginger during this period will be excluded from eligibility. However, once consented and commenced the intervention, participants who consume any ginger other than the study product will be included and concurrent consumption of oral ginger will be accounted for statistically. Participants will be regularly reminded to avoid consuming ginger and asked about any purposeful or incidental consumption.
• History of adverse reactions to ginger.
• Experiencing significant nausea and vomiting for reasons other than chemotherapy including:
o Prescribed medications with nausea-related side-effects, e.g. newly-prescribed opioids.
o Diagnosed with malignancies that might cause nausea and vomiting due to the position of the cancer e.g. gastrointestinal cancer.
o Metabolic risk factors for nausea e.g. electrolyte imbalances.
o Mechanical risk factors for nausea e.g. intestinal obstruction.
• Chronic alcohol use as indicated by >14 standard drinks per week (exceeding Australian Guidelines to Reduce Health Risks from Drinking Alcohol; predictive factor for decreased CIN risk).
• Severe thrombocytopenia or likely to experience severe thrombocytopenia (platelets <50 x 10^9/L) (medical note observation).
• Gallstones or liver disease (including liver cancer).
• Prescribed warfarin, anti-coagulant therapy, hypoglycaemics, insulin, cyclosporine, tacrolimus, and nonsteroidal anti-inflammatory drugs.
• Swallowing difficulties preventing supplement ingestion.
• Self-prescribed nausea therapies or complementary products.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The biostatistician (independent party - based at the NHMRC Clinical Trials Centre, University of Sydney) will notify the research assistant by telephone or email of the blinded number on the supplement label of each patient only after participants are deemed eligible.
To ensure blinding of participants, supplement and placebo capsules are over-encapsulated with a non-gelatin capsule and labelled by an independent third party, using a blinded sequence supplied by the biostatistician, prior to delivery to the study sites.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised into intervention and placebo groups (1:1) using the method of minimization, stratified by chemotherapy category (moderate vs. high emetogenicity), gender, age (<55, equal to or greater than 55 years), and by facility site. The randomization process is to be managed by an independent third party (biostatistician at the NHMRC Clinical Trials Centre, University of Sydney).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Baseline characteristics will be described and compared between groups using independent t-test analysis or Mann-Whitney U tests for continuous variables as appropriate, and chi-square for categorical variables. The primary outcome is the difference in the impact of nausea on QoL (CIN-related QoL as assessed by FLIE, continuous scale) at Day 5 (4-days post-chemotherapy) between the intervention and placebo groups. It will be calculated by an independent t-test as well as repeated measures (over the 3 chemotherapy cycles), based on mean differences between groups, adjusting for baseline. Multiple imputation will be used to input missing data for covariates and FLIE scores if ITT is applied. Adjusted results will be calculated using a multiple linear regression model including the stratification factors (recruitment site, emetogenicity, gender and age) and other known risk factors for nausea such as gender, age, anxiety, previous history of gestational nausea, and patient expectations of treatment. Secondary outcomes will also be analyzed at Day 5 (4-days post-chemotherapy) between the intervention and placebo groups and will be calculated based on mean differences, adjusting for baseline, using an independent t-test for continuous variables (global QoL, fatigue, PG-SGA score) and chi-square for categorical variables (PG-SGA global rating). The mean costs of each arm of the trial will be calculated and compared by combining the health service unit cost data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/07/2017
Actual
3/07/2018
Date of last participant enrolment
Anticipated
31/12/2019
Actual
31/12/2019
Date of last data collection
Anticipated
1/06/2020
Actual
30/04/2021
Sample size
Target
300
Accrual to date
Final
103
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9620 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 9621 0
Mater Adult Hospital - South Brisbane
Recruitment postcode(s) [1] 18376 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 18377 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 293107 0
Charities/Societies/Foundations
Name [1] 293107 0
Cancer Council Queensland
Country [1] 293107 0
Australia
Primary sponsor type
University
Name
Bond University
Address
Bond University, 14 University Drive, Robina, Queensland, 4226
Country
Australia
Secondary sponsor category [1] 291897 0
None
Name [1] 291897 0
none
Address [1] 291897 0
none
Country [1] 291897 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294608 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 294608 0
Ethics committee country [1] 294608 0
Australia
Date submitted for ethics approval [1] 294608 0
01/05/2017
Approval date [1] 294608 0
12/07/2017
Ethics approval number [1] 294608 0
HREC/17/QPAH/333

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64346 0
Prof Liz Isenring
Address 64346 0
Bond University, 14 University Drive, Robina, QLD 4226
Country 64346 0
Australia
Phone 64346 0
+61 7 5595 5530
Fax 64346 0
Email 64346 0
[email protected]
Contact person for public queries
Name 64347 0
Skye Marshall
Address 64347 0
Bond University, 14 University Drive, Robina, Queensland, 4226
Country 64347 0
Australia
Phone 64347 0
+61 7 5595 5530
Fax 64347 0
Email 64347 0
[email protected]
Contact person for scientific queries
Name 64348 0
Skye Marshall
Address 64348 0
Bond University, 14 University Drive, Robina, Queensland, 4226
Country 64348 0
Australia
Phone 64348 0
+61 7 5595 5530
Fax 64348 0
Email 64348 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.