Lian et al. (2014): Comparing the Effectiveness of Green Tea versus Topical Metronidazole Powder in Malodorous Control of Fungating Malignant Wounds in a Controlled Randomised Study

Reference ↗
Title	Comparing the Effectiveness of Green Tea versus Topical Metronidazole Powder in Malodorous Control of Fungating Malignant Wounds in a Controlled Randomised Stud
Topic	Green tea (EGCG)
Author	Lian, SB, Xu, Y, Goh, SL, Aw, FC
Year	2014
Journal	Proceedings of Singapore Healthcare
DOI	https://doi.org/10.1177/201010581402300102

Brief summary

In this study, 30 patients with malodorous malignant wounds were randomly assigned to one of two arms. In one arm the wounds were treated daily for 7 days with green tea bags and in the other arm with metronidazole powder (= antibiotic in powder form). Data was collected on the odour of the wounds, the patients' quality of life and wound healing. Overall, all patients from both arms showed a reduction in odour and an improvement in quality of life. There were no differences between the green tea arm and the metronidazole arm.. There was also no difference between the two arms with regard to the healing process. This shows that the treatment of wounds with green tea is just as effective as that with metronidazole. In addition, 8 patients from the green tea arm reported that they felt a cooling effect in the wound bed after cleaning with the green tea liquid. Overall, the study is convincing due to its good reporting and critical self-evaluation. Nevertheless, the short follow-up period and the inadequate group comparability with regard to the size of the wounds should be criticised. Furthermore, the study is not representative of all cancer patients, as these were seriously ill hospitalised patients.

In dieser Studie wurden 30 Patienten mit übelriechenden, bösartigen Wunden zufällig in eine von zwei Armen eingeteilt. Bei dem einen Arm wurden die Wunden täglich für 7 Tage mittels Grüntee-Beutel behandelt und in dem anderen Arm mittels Metronidazol-Puder (=Antibiotikum in Puderform). Es wurden Daten bezüglich des Geruchs der Wunden, der Lebensqualität der Patienten und der Wundheilung erhoben. Insgesamt zeigten alle Patienten aus beiden Gruppen eine Reduzierung des Geruchs und eine Verbesserung der Lebensqualität. Unterschiede zwischen dem Grüntee- und Metronidazol-Arm gab es diesbezüglich nicht. Es gab auch keinen Unterschied zwischen beiden Armen bezüglich des Heilungsprozesses. Somit hat sich gezeigt, dass die Behandlung der Wunden mit Grüntee genauso effektiv ist wie die mit Metronidazol. Außerdem berichteten 8 Patienten aus dem Grüntee-Arm, dass sie nach der Reinigung mit dem grünen Tee eine kühlende Wirkung im Wundbett verspürten. Insgesamt überzeugt die Studie durch ihre gute Berichterstattung und kritische Selbstbetrachtung. Dennoch ist die kurze Nachbeobachtungszeit und die nicht hinreichend gegebene Gruppenvergleichbarkeit bezüglich der Größe der Wunden kritisch anzumerken. Außerdem ist die Studie nicht für alle Krebspatienten repräsentativ, da es sich hier um schwer kranke hospitalisierte Patienten handelt.

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	NI
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	All hospitalised patients with malodorous fungating malignant wounds were eligible to participate in the study
Exclusion criteria	Fungating malignant wound with fistula, sinus or exposure of bone; patients receiving systemic metronidazole; patients treated with topical metronidazole for more than 30 days and neutropenic patients with total white cell count of less than 1.5×109/L.
N randomized	30
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	One patient in the green tea group did not complete the seven days of treatment as she died of advanced cancer on Day 5, the malodorous scores for Day 5 to Day 7 were conservatively assumed as per scored on Day 4. - Frequencies and percentages were calculated for categorical variables - Descriptive statistics were calculated for continuous variables - Wilcoxon ranksum test was used for statistical analysis to compare the malodorous scores between the two groups
Countries of data collection	Singapore
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	T0: Baseline T1: after 7 days

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	Diverse
Specifications on cancer therapies	The location of the fungating malignant wounds were breast (n=24), neck (n=2), groin (n=2), spine (n=1) and anus (n=1).
Previous cancer therapies	Diverse
Gender	Mixed
Gender specifications	Male n(%) per arm: Green tea arm: 2 (13), Metronidazole arm: 1 (7) Female n(%) per arm: Green tea arm: 13 (87), Metronidazole arm: 14 (93)
Age groups	Adults (18+)
Age groups specification	Age in years, median (min-max) per arm: Green tea arm: 55 (33-81), Metronidazole arm: 46 (35-81)

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	15
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	1
Drop-out reasons	Death due to advanced cancer on day 5
Intervention	Green Tea
Dosage and regime	Dressing Procedure 1. Irrigate wound with green tea solution with 20ml syringe until return flow is clear 2. Cover wound with absorbent pad(s) with dry green tea bag (insert within the absorbent pad) and secure with 2-inch micropore tape + Assigned nurse performs for all participants Day 1 and day 7: wound assessment; questionnaire on quality of life; photography of wound Day 1 to day 7: daily dressing; daily odour rating using VNS by patient and nurse independently
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.	7
Side effects / Interactions	No patient reported any side-effect and there was no adverse event regardless of the odour score

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention, Active control
Number of participants (arm) N randomized	15
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	Metronidazole
Dosage and regime	Dressing Procedure Irrigate wound with Normal Saline 0.9% with 20ml syringe until return flow is clear 1. Sprinkle metronidazole powder to wound bed (pound metronidazole tablet(s) finely) 2. Cover wound with absorbent pad(s) and secure with 2-inch micropore tape + Assigned nurse performs for all participants: Day 1 and day 7: wound assessment; questionnaire on quality of life; photography of wound Day 1 to day 7: daily dressing; daily odour rating using VNS by patient and nurse independently
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.	7
Side effects / Interactions	No patient reported any side-effect and there was no adverse event regardless of the odour score

Outcomes

"Questionaire" is not in the list (AQoL-8D (Assessment of Quality of Life), ASAT (Auditory Sustained Attention Test), BIA (Bioelectrical impedance analysis), BPI-SF (Brief Pain Inventory - Short Form), CTCAE (Common Terminology Criteria of Adverse Events), ESAS (Edmonton Symptom Assessment Scale), FAACT (Functional Assessment of Anorexia-Cachexia Therapy), FACIT (Functional Assessment of Chronic Illness Therapy), FLIE (Functional Living Index for Emesis), Genitourinary atrophy self-assessment tool, ...) of allowed values for the "Type of measurement" property.

"picture" is not in the list (AQoL-8D (Assessment of Quality of Life), ASAT (Auditory Sustained Attention Test), BIA (Bioelectrical impedance analysis), BPI-SF (Brief Pain Inventory - Short Form), CTCAE (Common Terminology Criteria of Adverse Events), ESAS (Edmonton Symptom Assessment Scale), FAACT (Functional Assessment of Anorexia-Cachexia Therapy), FACIT (Functional Assessment of Chronic Illness Therapy), FLIE (Functional Living Index for Emesis), Genitourinary atrophy self-assessment tool, ...) of allowed values for the "Type of measurement" property.

Wound odour

Outcome type As specificed by the authors	Primary
Outcome specification	Rating the odour on a scale of 0 to 10 (0= “no smell” and 10= “the worst smell that one can imagine”) by the patient and the same nurse independently upon removal of old dressing
Type of measurement	VNS (Verbal Numerical Scale)
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".	On day 7, 50% of the patients reported having complete eradication of odour; 9 of the patients were from the metronidazole arm and 6 patients were from the green tea arm
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".	All patients in both arms had shown reduction in malodorous score over 7 days of treatment. There was no significant difference in the improvement of odour in either arms (p>0.05).

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	?

Quality of life

Outcome type As specificed by the authors	Primary
Outcome specification	Five-item questionnaire developed by the researchers who are trained in oncology nursing; were rated on a VNS of 0 to 10 (0´= being the healthiest attribute and 10 = being the worst) at day 1 and day 7
Type of measurement	VNS (Verbal Numerical Scale)
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".	NI
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".	All patients reported an improvement in odour control after day 7 (p=0.00), impairment of daily life (p=0.00), physical discomfort (p=0.00), appetite (p=0.00) and social activities (p=0.00); but there are no significant differences between the two arms (p>0.05), except for Q5. The green tea arm rated that the odour from their wounds had significantly impacted (p=0.04) their social activities prior to treatment.

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	?

Wound healing

Outcome type As specificed by the authors	Primary
Outcome specification	Taking a picture using a digital camera on day 1 and day 7; provides an objective assessment of the healing progress of the wound in term of its size, type and amount of necrotic tissues, and amount of exudates
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".	Sizes of fungating wounds in the green tea arm were significantly larger (p<0.04) than wounds in the metronidazole arm. There was no significant difference in the type and amount of necrotic tissue.
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".	Pre and post treatment assessment of the wound size, necrotic tissue and type showed no statistical significance (p>0.05). There were no significant differences between the two arms.

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	The study was funded by the Ministry of Health and Care.
Conflicts of Interest	The study was funded by the Ministry of Health and Care.

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	?