A Comparative Investigation of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis

Study Overview
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Brief Summary
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To compare the performance of standard of care (SOC) + episil® versus SOC alone on oral mucositis in patients receiving conditioning treatment for hematopoietic stem cell transplantation (HSCT). The primary variable will be the area under the curve (AUC) of oral mucositis scores defined by the World Health Organisation (WHO) oral toxicity scale assessed daily by the investigator over the 28-day study period.

Detailed Description
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This was multicentre, open-label, randomised parallel-group study. Patients were randomised to one of two parallel treatment groups: episil® in combination with SOC or SOC alone. The study was originally planned to be conducted in several sites in the following countries: Denmark, Israel, Poland, and Sweden. Following a country-specific Amendment on 20-Feb-2013 and a German Ethical Committee (EC) approval in 07-May-2013, Germany was added to the list of countries where the study would be conducted. No study sites were initiated in Denmark. The study design was aimed to facilitate direct comparison of the performance of SOC + episil® versus SOC alone. The study was conducted in an open-label manner that is common in trials involving cancer patients, as this takes into the account the ethical issues involved in this indication and patient population. To reduce the likelihood of bias, assignment to study treatment was randomised. SOC as control group is appropriate and widely used, especially in trials involving cancer patients. In this particular study, basic oral hygiene consisting of brushing, flossing, rinsing and moisturising was taken as the SOC used as control group. .

Official Title
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A Multicenter, Open-label, Parallel Group Investigation to Compare the Performance of Standard Of Care (SOC) and Episil® in Combination Versus SOC Alone on Oral Mucositis in Patients Receiving Conditioning Treatment for Hematopoietic Stem Cell Transplantation

Conditions
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Oral Mucositis

Intervention / Treatment
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* Device: episil(R)
* Other: Oral hygiene procedures


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is at least 18 years of age. Has a confirmed diagnosis for which he/she is scheduled for hematopoietic stem cell transplantation (HSCT) of either type of transplant (autologous or allogeneic). Is due to undergo treatment with myeloablative conditioning (radiation-based or non radiation based) before HSCT. Exclusion Criteria: Will undergo reduced intensity conditioning before HSCT. Has got known allergy to any ingredient in the study product or to peanuts, peppermint oil, or soya. Is pregnant or breast feeding. Has any other concurrent medical condition that, in the opinion of the investigator, would increase the risk to the patient, compromise evaluation of the investigational device, or interfere with the conduct of the study. Has an unstable condition (eg, a psychiatric disorder, a recent history of substance abuse) or is otherwise thought to be unreliable or incapable of complying with the study requirements. Is undergoing treatment with parenteral opioids at enrolment. Uses treatments that promote mucosal healing (eg, palifermin). Uses electrolyte mouthwashes (eg, Caphosol®) or other topical oral treatments (eg, Tantum Verde® (benzydamine), Gelclair®, Fungicidin (nystatin)).

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard-Of-Care + episil(R)<br>Standard-Of-Care plus episil® administered as three consecutive pump-strokes for a total volume of 0.45 mL applied 3 times daily and additionally, as needed | Device: episil(R)<br>* episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.<br>Other: Oral hygiene procedures<br>* Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)<br>|
| Other: Standard-Of-Care<br>Oral hygiene procedures | Other: Oral hygiene procedures<br>* Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population | Summary of WHO (World Health Organisation) Oral Toxicity Scores Area under the curve (AUC) over the 28-Day Period ITT Populations. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days | 
| WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population | Summary of WHO (World Health Organisation) Oral Toxicity Scores AUC Over the 28-Day Period Per protocol population. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Oral Mucositis | Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organization) oral toxicity scale grade 0-4. A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days | 
| Duration of Oral Mucositis, Intention to Treat Population | Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis was graded according to WHO 5 Point grading scale on a daily basis. Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days | 
| Oral Mucositis Daily Questionnaire (OMDQ) | OMDQ (Oral Mucositis Daily Questionnaire) scale was used to measure Overall Mouth and Throat Soreness This was scored from 0=no soreness to 10=worst possible soreness. | 28 days | 
| Oral Mucositis Assessment Scale (OMAS) | Summary of Oral Mucositis Assessment Scale (OMAS) Ulceration and Erythema Scores Extent of ulceration (grade 0-3) and severity of erythema (grade 0-2) according to the OMAS (Oral Mucositis Assessment Scale) assessed by a dental practitioner twice-weekly over the 28-day study period. The extent of ulceration was rated as follows: 0 no lesion 1 cm2 1-3 cm2 >3 cm2 The severity of erythema was assessed as follows: 0 none not severe severe | 28 days | 
| Hospital Stay, Days | Duration of hospital stay (time from admission to discharge) | 28 days | 
| Occurence of Oral Mucositis, Per Protocol Population | Occurrence of oral mucositis (ie, oral mucositis defined as WHO (World Health Organisation) oral toxicity scale grade 0-4 A higher score represents a more severe oral mucositis Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days | 
| Duration of Oral Mucositis, Per Protocol Population | Duration of oral mucositis during the treatment period of 28 Days. Oral mucositis is graded according to the 5-point oral mucositis WHO scale Grade 0 No mucositis Grade 1 Soreness ± erythema, no ulceration Grade 2 Erythema, ulcers. Patients can swallow solid diet Grade 3 Ulcers, extensive erythema. Patients cannot swallow solid diet Grade 4 Oral mucositis to the extent that alimentation is not possible | 28 days |