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

• ClinicalTrials.gov Identifier: NCT01684566
• Recruitment Status: Completed
• First Posted: September 13, 2012
• Results First Posted: March 14, 2016
• Last Update Posted: March 14, 2016
• Sponsor: Camurus AB
• Information provided by (Responsible Party): Camurus AB

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Oral Mucositis	Device: episil(R); Other: Oral hygiene procedures	Not Applicable

Detailed Description:

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.

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: 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
• Study Start Date: February 2013
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Standard-Of-Care + episil(R); 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); episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.; Other: Oral hygiene procedures; Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Standard-Of-Care; Oral hygiene procedures	Other: Oral hygiene procedures; Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)

Outcome Measures

Primary Outcome Measures :

1. WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population [ Time Frame: 28 days ]

   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

2. WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population [ Time Frame: 28 days ]

   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

Secondary Outcome Measures :

1. Occurrence of Oral Mucositis [ Time Frame: 28 days ]

   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

2. Duration of Oral Mucositis, Intention to Treat Population [ Time Frame: 28 days ]

   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

3. Oral Mucositis Daily Questionnaire (OMDQ) [ Time Frame: 28 days ]
   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.
4. Oral Mucositis Assessment Scale (OMAS) [ Time Frame: 28 days ]

   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. 1 cm2
   2. 1-3 cm2
   3. >3 cm2

   The severity of erythema was assessed as follows:

   0 none

   1. not severe
   2. severe
5. Hospital Stay, Days [ Time Frame: 28 days ]
   Duration of hospital stay (time from admission to discharge)
6. Occurence of Oral Mucositis, Per Protocol Population [ Time Frame: 28 days ]

   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

7. Duration of Oral Mucositis, Per Protocol Population [ Time Frame: 28 days ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Is at least 18 years of age.
2. Has a confirmed diagnosis for which he/she is scheduled for hematopoietic stem cell transplantation (HSCT) of either type of transplant (autologous or allogeneic).
3. Is due to undergo treatment with myeloablative conditioning (radiation-based or non radiation based) before HSCT.

Exclusion Criteria:

1. Will undergo reduced intensity conditioning before HSCT.
2. Has got known allergy to any ingredient in the study product or to peanuts, peppermint oil, or soya.
3. Is pregnant or breast feeding.
4. 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.
5. 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.
6. Is undergoing treatment with parenteral opioids at enrolment.
7. Uses treatments that promote mucosal healing (eg, palifermin).
8. Uses electrolyte mouthwashes (eg, Caphosol®) or other topical oral treatments (eg, Tantum Verde® (benzydamine), Gelclair®, Fungicidin (nystatin)).

Contacts and Locations

Locations

Germany

Med Klinik und Poliklinik I Universitatsklinikum Carl Gustav Carus

Dresden, Germany, 01307

Abteilung fur Hamatologie und Onkologie Universitatsmedizin an der Georg-August-Universitat

Gottingen, Germany, 37099

Israel

Rambam Health Care Campus

Haifa, Israel, 31096

Hadassah Medical Centre

Jerusalem, Israel, 91240

Rabin Medical Center

Petah Tikva, Israel, 49100

The Tel-Aviv Sourasky Medical Centre

Tel Aviv, Israel, 64239

Poland

Military Institute of Medicine Internal diseases and Haemtalogy Clinic

Warszawa, Poland, 01141

Institute of Haematology and Transfusion Medicine

Warszawa, Poland, 02776

Oncology Center Institute named Maria Sklodowska-Curie Lymph System Cancer Clinic

Warszawa, Poland, 02781

Sweden

Karin Garming-Legert

Stockholm, Huddinge, Sweden, 141 04

Lund University Hospital

Lund, Sweden, 22185

Uppsala University Hospital

Uppsala, Sweden, 75185

Sponsors and Collaborators

Camurus AB

Investigators

• Principal Investigator: Karin Garming-Legert, DDS, PhD.; Karolinska Institutet, Stockholm, Sweden

More Information

• Responsible Party: Camurus AB
• ClinicalTrials.gov Identifier: NCT01684566
• Other Study ID Numbers: HS-10-396
• First Posted: September 13, 2012
• Results First Posted: March 14, 2016
• Last Update Posted: March 14, 2016
• Last Verified: November 2015

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Mucositis; Stomatitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases