Efficacy of Propolis in the Prevention of Oral Mucositis

Study Overview
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Brief Summary
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The study was carried out to determine the efficacy of propolis in the prevention of oral mucositis and gastrointestinal symptoms associated with oral mucositis in patients with leukemia, lymphoma, and myelodysplastic syndrome receiving high-dose chemotherapy and/or hematopoietic stem cell transplantation. 64 patients, 32 in the propolis and 32 in the control group, were involved in the prospective randomized controlled experimental study. While the standard oral care treatment protocol of the clinic was administered to the control group, aqueous propolis extract was applied to the propolis group in addition to the standard oral care treatment protocol.

Detailed Description
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Objective: The study was carried out to determine the efficacy of propolis in the prevention of oral mucositis and gastrointestinal symptoms associated with oral mucositis in patients with leukemia, lymphoma, and myelodysplastic syndrome receiving high-dose chemotherapy and/or hematopoietic stem cell transplantation. Study Design: The study was conducted as a randomized controlled experimental study. Approval from the Ethics Committee and written permission from the Institution were obtained. After the participants were informed about the purpose of the study, their written consents were obtained. 64 patients, 32 in the propolis and 32 in the control group were involved in the study that was performed in the Hematology and Bone Marrow Transplantation Unit. The control group patients used the standard oral care treatment protocol (Tanflex (3x1) and NaHCO3 (1x1)) of the clinic , while the propolis group used the aqueous extract of propolis in addition to this protocol. The individuals in the propolis group gargled 4 times a day (after meals and before going to bed at night) with 5 ml aqueous propolis extract. All patients underwent a daily intraoral examination up to 21 days from the start of high dose chemotherapy. Oral mucositis was recorded on the WHO oral toxicity scale and other gastrointestinal symptoms were recorded on the National Cancer Institute-Common Terminology Criteria for Adverse Events scale

Official Title
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Determination of the Effectiveness of Propolis in the Prevention of Oral Mucositis in Patients Receiving High Dose Chemotherapy: A Randomized Controlled Trial

Conditions
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Oral Mucositis

Intervention / Treatment
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* Other: Aqueous propolis extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Ability to communicate verbally Not having a diagnosed psychiatric disease Receiving inpatient high dose chemotherapy (diagnosed with leukemia, lymphoma and MDS) Hematopoietic Stem Cell Transplantation patients Zero OM score according to the World Health Organization Oral Toxicity Scale (WHOOTS) Karnofsky Performance Scale (KPS) score of 80 and above Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group, two arm, prospective randomized controlled clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aqueous propolis extract<br>The individuals in the intervention group were asked to gargle with 5 ml aqueous propolis extract four times a day after meals (morning, noon, evening and night before bedtime) and wait average one minute in the mouth and then spit, in addition to the standard practice of the clinic. According to the standard practice of the clinic, it was performed tanflex (3x1) and/or sodium bicarbonate (1x1) to the patients in the prevention of oral mucositis with the request of the physician. The patients were followed for 21 days. The 21-day period is consistent with the duration of mucositis healing in the literature. Follow-up and evaluation of patients who were discharged early were performed by home visits and made a phone call everyday. | Other: Aqueous propolis extract<br>* The patients gargled 4 times a day after meals and 5 ml each time. Patients were instructed to keep the propolis solution in their mouth for one minute, to touch all structures in the mouth, and not to eat or drink anything orally for one hour after spitting.<br>|
| No Intervention: Control<br>Standard procedures of the clinic were applied to control group. According to the standard practice of the clinic, it was performed tanflex (3x1) and/or sodium bicarbonate (1x1) to the patients in the prevention of oral mucositis with the request of the physician. Follow-up and evaluation of patients who were discharged early were performed by home visits and made a phone call everyday. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of oral mucositis | Time to onset of oral mucositis was be evaluated by the World Health Organization Oral Toxicity Scale which record the extent and severity of oral mucositis every day. The World Health Organization Oral Toxicity Scale: range 0 to 4, Grade 0; none, Grade 1; mild, Grade 2; moderate, Grade 3; severe, Grade 4; life threatening | For 21 days from the beginning of the chemotherapy | 
| Incidence of oral mucositis | Incidence of oral mucositis was be evaluated by the World Health Organization Oral Toxicity Scale which record the extent and severity of oral mucositis every day. The World Health Organization Oral Toxicity Scale: range 0 to 4, Grade 0; none, Grade 1; mild, Grade 2; moderate, Grade 3; severe, Grade 4; life threatening | For 21 days from the beginning of the chemotherapy | 
| Severity of oral mucositis | Severity of oral mucositis was be evaluated by the World Health Organization Oral Toxicity Scale which record the extent and severity of oral mucositis every day. The World Health Organization Oral Toxicity Scale: range 0 to 4, Grade 0; none, Grade 1; mild, Grade 2; moderate, Grade 3; severe, Grade 4; life threatening | For 21 days from the beginning of the chemotherapy | 
| The duration of oral mucositis | The duration of oral mucositis was be evaluated by the World Health Organization Oral Toxicity Scale which record the extent and severity of oral mucositis every day. The World Health Organization Oral Toxicity Scale: range 0 to 4, Grade 0; none, Grade 1; mild, Grade 2; moderate, Grade 3; severe, Grade 4; life threatening | From day 1 to day 21 of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of at least grade 2 oral mucositis | Time to onset of at least grade 2 oral mucositis was be evaluated by the World Health Organization Scale which record the extent and severity of oral mucositis every day. The World Health Organization Oral Toxicity Scale: Grade 2; moderate, Grade 3; severe and Grade 4; life threatening | From day 1 to day 21 of chemotherapy | 
| Time to onset of dry mouth | Time to onset of dry mouth was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | From day 1 to day 21 of chemotherapy | 
| Incidence of dry mouth | Incidence of dry mouth was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Severity of dry mouth | Severity of dry mouth was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| The duration of dry mouth | The duration of dry mouth was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Time to onset of nausea | Time to onset of nausea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | From day 1 to day 21 of chemotherapy | 
| Incidence of nausea | Incidence of nausea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Severity of nausea | Severity of nausea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| The duration of nausea | The duration of nausea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Time to onset of sensitivity/pain in the gums | Time to onset of sensitivity/pain in the gums was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | From day 1 to day 21 of chemotherapy | 
| Incidence of sensitivity/pain in the gums | Incidence of sensitivity/pain in the gums was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Severity of sensitivity/pain in the gums | Severity of sensitivity/pain in the gums was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| The duration of sensitivity/pain in the gums | The duration of sensitivity/pain in the gums was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Time to onset of pain in the oral mucosa | Time to onset of pain in the oral mucosa was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Incidence of pain in the oral mucosa | Incidence of pain in the oral mucosa was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Severity of pain in the oral mucosa | Severity of pain in the oral mucosa was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| The duration of pain in the oral mucosa | The duration of pain in the oral mucosa was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Time to onset of dysphagia | Time to onset of dysphagia was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Incidence of dysphagia | Incidence of dysphagia was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Severity of dysphagia | Severity of dysphagia was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| The duration of dysphagia | The duration of dysphagia was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Time to onset of esophagitis | Time to onset of esophagitis was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Incidence of esophagitis | Incidence of esophagitis was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Severity of esophagitis | Severity of esophagitis was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| The duration of esophagitis | The duration of esophagitis was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Time to onset of diarrhea | Time to onset of diarrhea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Incidence of diarrhea | Incidence of diarrhea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Severity of diarrhea | Severity of diarrhea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| The duration of diarrhea | The duration of diarrhea was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 5, 1 was the mild, 5 was the death | For 21 days from the beginning of the chemotherapy | 
| Time to onset of weight loss | Time to onset of weight loss was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Incidence of weight loss | Incidence of weight loss was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| Severity of weight loss | Severity of weight loss was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 
| The duration of weight loss | The duration of weight loss was be evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Events Scale which to describe the severity of organ toxicity for patients receiving cancer therapy every day. The National Cancer Institute Common Terminology Criteria for Adverse Events Scale: Range 1 to 3, 1 was the mild, 3 was the severe | For 21 days from the beginning of the chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Mucositis, Propolis, High Dose Chemotherapy