Propolis-based Product (FARINGEL PLUS) for Oral Mucositis in Palliative Care

Study Overview
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Brief Summary
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Oral health is crucial for palliative patients' quality of life. The evidence on effective interventions and measures of oral mucositis in palliative care is sparse. This is a single-center, prospective, uncontrolled open label Phase 2 non-profit study, aimed at evaluating a propolis-based product (FARINGEL PLUS) added to basic oral hygiene safety, acceptability and activity in preventing and treating oral mucositis in patients in palliative care. A two-step design was adopted according to Simon's Optimum approach, with an overall sample of 77 evaluable cases (step1_26 cases; step2_51 cases).

Detailed Description
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Palliative Care with has primary objective of the best possible quality of life for patients with advanced illness. Oral health is crucial for quality of life. Oral disorders such as hyposalivation, mucositis, erythema, ulceration and viral and fungal infections, can cause annoying symptoms such as dry mouth, dysphagia, dysgeusia, orofacial pain and speech difficulties, which negatively affect nutrition, verbal communication, social interaction and sleep. An Italian study of advanced cancer patients in palliative care found a prevalence of oral mucositis of 22%, of dysphagia of 15% and of dry mouth of 40%. Studies on interventions aimed at preventing and treating oral mucositis in palliative care are scarse and no standard oral protocol can be recommended. Moreover, there are no known scales specifically developed and validated for the evaluation of mucositis and other disorders of the oral cavity in palliative care. Propolis has historically been used as folk medicine due to multiple biological properties, such as anesthetic, antimicrobial, antifungal, antiviral, and anti-inflammatory for the oral and pharyngeal mucosa. Propolis is effective in reducing the severity of radiation-induced oral mucositis in animals, is associated with a significant reduction in the number and size of oral ulcers in patients diagnosed with recurrent stomatitis and with complete recovery from denture-related stomatitis, and is found safe, acceptable and with promising efficacy in preventing oral mucositis in patients undergoing chemotherapy for breast cancer. In particular, an oral suspension based on propolis (Faringel) and containing aloe vera gel, calendula, chamomile and sodium alginate, has been found to be well accepted, safe and promising in the prevention of severe oesophagitis from radiotherapy in patients with lung cancer. Hyaluronic acid (Faringel plus) has recently been added to this suspension with a re-epithelizing function on the mucous membranes. Therefore, we planned this single-center, prospective, uncontrolled open label Phase 2 non-profit study aimed at evaluating whether the addition of a propolis-based product (FARINGEL PLUS) to a basic oral hygiene protocol can be safe, acceptable and active in the protection of the oral cavity in patients in palliative care. To verify this hypothesis, a two-step design was adopted according to Simon's Optimum design approach. An overall sample of 77 evaluable cases was defined (step1_26 cases; step2_51 cases).

Official Title
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Sicurezza ed Efficacia di un Prodotto a Base di Propoli (FARINGEL PLUS) Nella Prevenzione e Nel Trattamento Della Mucosite Orale in Pazienti in Cure Palliative: Uno Studio di Fase 2

Conditions
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Oral Mucositis

Intervention / Treatment
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* Combination Product: Faringel plus and oral hygiene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients cared for by specialized palliative care center in hospice or at home Conscious patients able to swallow (score 1-2 at the swallowing item of OAG) Patients with a life expectancy of between one week and one month estimated with the RAD (Approximation of Death Recognition) card in use in the palliative care center where the study will be conducted; Patients who provide consent to participate in the study and use the data independently, or through their legal representative. Exclusion Criteria: Patients with a life expectancy of less than one week or more than one month estimated with the RAD (Approximation of Death Recognition) card; Patients who are unable to swallow (score 3 on the swallowing item on the OAG scale) Patients with head / neck cancer or tracheostomy; Patients who report allergy to propolis, honey, aloe, chamomile, calendula, stevia (or other components of the product under study) or atopy.

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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Two-step design according to Simon's Optimum approach (1989). Overall sample = 77 evaluable cases (step1_26 cases; step2_51 cases). Parameters: P0 (minimum probability of response): 0.45; P1 (probability of optimal response): 0.60; Alpha: 5%; Power: 80%.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phase 2 open intervention<br>All patients assisted by the palliative care center (hospice and home) will receive the oral hygiene protocol and the propolis-based product. The oral hygiene protocol will be applied starting from the day of taking care of the patient in the service and until discharge / death. Administration of the study product will be continued for 2 weeks or stopped sooner if the patient loses the ability to swallow. | Combination Product: Faringel plus and oral hygiene<br>* The expected frequency of administration of the study product is 2 / day, 10 minutes 'before main meals, for patients without mucositis (grade 1 according to the OAG scale, total score = 8). The frequency of administration will increase to 3 / day for patients with mild or moderate mucositis (grade 2 on the OAG scale, total score 9-18) and up to 4 / day in cases of severe mucositis (grade 3 on the OAG scale, score total 19-24). Each administration will contain 7 ml of oral suspension, to be kept inside the oral cavity for 1-2 minutes and then swallowed slowly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of oral mucositis | Reduction of the severity of mucositis by at least one degree, or maintenance of the normal condition, measured by the elements of the OAG scale whose score indicates 3 degrees (from 1 normal condition to 3 severe mucositis). The minimum grade achieved during the patient's stay in the study will be considered. | daily up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| orpharyngeal pain | Appearance and severity of oropharyngeal pain assessed with a Numerical Rating Scale (NRS), from 0 to 10 meaning 0 the absence of pain and 10 the worst pain imaginable | daily up to 15 days | 
| esophageal pain | Appearance and severity of esophageal pain assessed with a Numerical Rating Scale (NRS), from 0 to 10 meaning 0 the absence of pain and 10 the worst pain imaginable | daily up to 15 days | 
| dysgeusia | Dysgeusia assessed with a Numerical Rating Scale (NRS), from 0 to 10 meaning 0 the absence of symptom and 10 the worst symptom imaginable | daily up to 15 days | 
| ability to swallow, voice condition, feeling of dry mouth | ability to swallow, voice condition, feeling of dry mouth assessed through the Oral Assessment Guide (OAG - Eilers 1988; D'Angelo et al., 2013) at 3 levels of severity (from 1 normal condition, 2 mild disorders / moderate, 3 severe disorders) and the Tardieu scale, at 4 levels of severity, where 0 is normal and 3 is the maximum degree of alteration). | daily up to 15 days | 
| Oral fungal infections | Presence and severity of fungal infections measured with CTC-AE (grade 0-5) | daily up to 15 days | 
| Duration of oral disorders | Duration of oral cavity disorders measured in days and defined from the moment in which a degree different from normality occurs until the first evaluation with return to normality; | daily up to 15 days | 
| Comfort during feeding | Alteration of comfort during feeding measured daily with a Numerical Rating Scale (NRS), from 0 to 10 (0 complete absence of comfort and 10 maximum comfort) | daily up to 15 days | 
| Meal completion rate | Food pattern compared to that of the 3 previous days and to the normal situation, measured in number of meals per day and average percentage of completion of individual meals | daily up to 15 days | 
| Patient quality of life | Quality of life measured at time 0 and then every 3 days with the European Quality of Life Utility Scale (EQ-5D) | Every 3 days up to 15 days | 
| Patient oral-related quality of life | Oral-related quality of life measured with the Oral Mucositis Daily Questionnaire (OMDQ) | Daily up to 15 days | 
| Adherence to intervention | Adherence to oral care and to administration of the product under study recorded daily as frequency, type and quantity | daily up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palliative care, Hospice, Home palliative care, Oral assessment guide