Oral Mucositis
Conditions
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.
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. .
Interventions
DEVICEepisil(R)
episil® is a lipid-based liquid that spreads onto mucosal surfaces and transforms into a protective, strongly bioadhesive FluidCrystal® film after intraoral administration.
OTHEROral hygiene procedures
Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available)
Sponsors
Camurus AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population | 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 |
| WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population | 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
| Measure | Time frame | Description |
|---|---|---|
| Oral Mucositis Daily Questionnaire (OMDQ) | 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. |
| Oral Mucositis Assessment Scale (OMAS) | 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 |
| Occurrence of Oral Mucositis | 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 |
| Occurence of Oral Mucositis, Per Protocol Population | 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 |
| Duration of Oral Mucositis, Per Protocol Population | 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 |
| Hospital Stay, Days | 28 days | Duration of hospital stay (time from admission to discharge) |
| Duration of Oral Mucositis, Intention to Treat Population | 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 |
Countries
Germany, Israel, Poland, Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
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.
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available) | 57 |
| Standard-Of-Care Oral hygiene procedures
Oral hygiene procedures: Oral hygiene by using toothbrush, toothpaste, lip balm and dental floss (if available) | 52 |
| Total | 109 |
Baseline characteristics
| Characteristic | Standard-Of-Care + Episil(R) | Total | Standard-Of-Care |
|---|---|---|---|
| Age, Continuous | 46.4 years STANDARD_DEVIATION 15.21 | 47.6 years STANDARD_DEVIATION 15.01 | 49.0 years STANDARD_DEVIATION 14.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 56 Participants | 107 Participants | 51 Participants |
| Region of Enrollment Germany | 10 participants | 17 participants | 7 participants |
| Region of Enrollment Israel | 23 participants | 46 participants | 23 participants |
| Region of Enrollment Poland | 13 participants | 26 participants | 13 participants |
| Region of Enrollment Sweden | 11 participants | 20 participants | 9 participants |
| Sex: Female, Male Female | 27 Participants | 42 Participants | 15 Participants |
| Sex: Female, Male Male | 30 Participants | 67 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 57 | 23 / 52 |
| serious Total, serious adverse events | 4 / 57 | 1 / 52 |
Outcome results
Primary
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
Time frame: 28 days
Population: Intention to treat (ITT) and Last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population | 0.63 score | Standard Deviation 0.702 |
| Standard-Of-Care | WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Intention to Treat Population | 0.56 score | Standard Deviation 0.589 |
Primary
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
Time frame: 28 days
Population: Per Protocol (PP) without Last observation carried over(LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population | 0.39 score | Standard Deviation 0.402 |
| Standard-Of-Care | WHO (World Health Organisation) Oral Mucositis Severity Score During 28 Days of Treatment, Per Protocol Population | 0.56 score | Standard Deviation 0.587 |
Secondary
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
Time frame: 28 days
Population: ITT (Intention to treat). There were13 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | Duration of Oral Mucositis, Intention to Treat Population | 9.5 Days | Standard Deviation 6.85 |
| Standard-Of-Care | Duration of Oral Mucositis, Intention to Treat Population | 10.7 Days | Standard Deviation 6.03 |
Secondary
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
Time frame: 28 days
Population: Per Protocol (PP). There were 9 patients in the episil +SOC group and 12 patients in the SOC group who had no data for duration of oral mucositis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | Duration of Oral Mucositis, Per Protocol Population | 7.4 Days | Standard Deviation 5.85 |
| Standard-Of-Care | Duration of Oral Mucositis, Per Protocol Population | 10.1 Days | Standard Deviation 5.58 |
Secondary
Hospital Stay, Days
Duration of hospital stay (time from admission to discharge)
Time frame: 28 days
Population: Intention to treat (ITT) Hospital stay, days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | Hospital Stay, Days | 23.7 Days | Standard Deviation 4.45 |
| Standard-Of-Care | Hospital Stay, Days | 24.5 Days | Standard Deviation 3.43 |
Secondary
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
Time frame: 28 days
Population: Per Protocol (PP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard-Of-Care + Episil(R) | Occurence of Oral Mucositis, Per Protocol Population | 28 participants |
| Standard-Of-Care | Occurence of Oral Mucositis, Per Protocol Population | 37 participants |
Secondary
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
Time frame: 28 days
Population: Intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard-Of-Care + Episil(R) | Occurrence of Oral Mucositis | 44 participants |
| Standard-Of-Care | Occurrence of Oral Mucositis | 40 participants |
Secondary
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. 1 cm2 2. 1-3 cm2 3. \>3 cm2 The severity of erythema was assessed as follows: 0 none 1. not severe 2. severe
Time frame: 28 days
Population: Intention to treat (ITT) Ulceration and Erythema.OMAS was only performed in sites were a dentist was available therefore lower numbers in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard-Of-Care + Episil(R) | Oral Mucositis Assessment Scale (OMAS) | Ulceration | 0 score | Standard Deviation 0.21 |
| Standard-Of-Care + Episil(R) | Oral Mucositis Assessment Scale (OMAS) | Erythema | 0.3 score | Standard Deviation 0.7 |
| Standard-Of-Care | Oral Mucositis Assessment Scale (OMAS) | Erythema | 0.5 score | Standard Deviation 1.39 |
| Standard-Of-Care | Oral Mucositis Assessment Scale (OMAS) | Ulceration | 0 score | Standard Deviation 0.2 |
Secondary
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.
Time frame: 28 days
Population: Intention to treat(ITT) OMDQ AUC over time. Not all patients reported data from OMDQ therefore there is lower number of patients in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard-Of-Care + Episil(R) | Oral Mucositis Daily Questionnaire (OMDQ) | 2.59 units on a scale | Standard Deviation 1.619 |
| Standard-Of-Care | Oral Mucositis Daily Questionnaire (OMDQ) | 2.64 units on a scale | Standard Deviation 1.539 |