Clinical trial NCT01789658: Cryotherapy for Prevention of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation
Official title: A Randomized Controlled Trial of Cryotherapy for Prevention and Reduction of Severity of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Oral Mucositis
Pain
Infection
Nutrition Aspect of Cancer
Keywords: Oral Mucositis
Children
Cryotherapy
Hematopoietic Stem Cell Transplantation
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: The Swedish Childhood Cancer Foundation
First posted: 2013-02-12
Enrollment: 53
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Oral mucositis (OM) is a common adverse effect of chemotherapy, radiotherapy and conditioning regimens before Hematopoietic Stem Cell Transplantation (HSCT). The aim of this study is to effectiveness of cryotherapy as a prophylactic treatment in children undergoing HSCT.

Detailed description: There is a complex pathobiology behind OM; chemo and radiotherapy affects the mucosa and submucosa causing DNA-strand brakes and generation of reactive oxygen species (ROS). This initiates a cascade of events, among others activation of transcription factors, up-regulation of pro-inflammatory cytokines, and activation of macrophages and proteases leading to tissue injury causing symptoms such as erythema, edema, ulceration, taste perception alterations, and mouth dryness. OM often causes local and systemic infections, fatigue, pain, and difficulties in basal functions such as swallowing (and hence drinking and eating) and talking and reduces patients' psychological well-being. Nearly 90 % of pediatric patients undergoing HSCT are afflicted with OM. In pediatric patients mucositis is reported as one of the most painful and debilitating side effects during cancer treatment.Beyond a significant suffering for the patient it is hence associated with higher costs for health care and increased mortality.

The current scientific situation regarding prevention and treatment of OM has been summarized in Cochrane reports showing limited data on adults and practically missing data on children and adolescents. Concluding guidelines from these reports emphasize the need for well conducted randomized controlled trials (RCT's) to evaluate and refine treatments in order to establish evidence based interventions.

The use of cryotherapy to prevent oral mucositis in patients who are receiving high-dose chemotherapy as a conditioning agent prior to HSCT continue to show evidence in the adult population.

The aim of this study is to compare treatment with cryotherapy (Arm 1)with a standard oral care protocal (Arm 2)

ARM 1 Children are instructed to use chew on ice-chips, ingest ice-cream or ice-water during infusion of chemotherapy as part of the conditioning treatment prior to HSCT. Melted ice should be replaced by new as soon as possible. Children receiving a 24-hour infusion are instructed to use cryotherapy for one hour 4 times a day.

ARM 2 Standard care for prevention and management of oral mucositis

Primary outcome

* Degree and duration of Oral mucositis

Secondary outcomes

* Oral pain
* Opioid use
* Duration of parenteral nutrition
* Weight loss
* Duration of neutropenic fever
* Duration of antibiotic treatment
* Duration of hospitalization
* Emotional and psychological status
* C reactive protein (CRP) and s-albumin correlation to grade of Oral Mucositis

Eligibility criteria: Inclusion Criteria:

Age between 4-18 Undergoing Hematopoietic Stem Cell Transplantation in Sweden sufficient knowledge in swedish to understand the protocols -

Exclusion Criteria:

-

Primary outcomes:
measure: Mucositis grade - WHO Oral Toxicity Scale
timeFrame: Daily until engraftment, an expected average of 20 days.
Secondary outcomes:
measure: Mucositis grade - Children´s International Mucositis Evaluation Scale (ChiMES)
timeFrame: Daily until engraftment, an expected average of 20 days.
measure: Pain - Childrens Hospital Eastern Ontario Pain Scale (CHEOPS)
timeFrame: Daily until Engraftment an expected average of 20 days.
measure: Mouth Pain
timeFrame: Daily until Engraftment an expected average of 20 days
measure: Emotional and Psychological status
timeFrame: Daily until engraftment, an expected average of 20 days.
Other outcomes:
measure: Opioid consumption
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: Duration of parenteral nutrition
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: Weight Loss
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: Duration of Antibiotic treatment
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: Duration of febrile neutropenia
timeFrame: Until engraftment, an expected average of 20 days
measure: Duration of Hospitalisation
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: C reactive protein
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
measure: S-Albumin
timeFrame: During hospitalization in connection with HSCT, an expected average of 25 days
Locations:
city: Gothenburg
country: Sweden
facility: Pediatric Oncology Department, Queen Silvia Childrens´ Hospital
city: Lund
country: Sweden
facility: Departent of Pediatric Oncology, Lund University Hospital
city: Stockholm
country: Sweden
facility: Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Hudding
city: Stockholm
country: Sweden
facility: Department of pediatrics B78, Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Department of Hematology, Uppsala University Hospital
Study officials:
affiliation: Uppsala University
name: Gustaf Ljungman, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kamsvag T, Svanberg A, Legert KG, Arvidson J, von Essen L, Mellgren K, Toporski J, Winiarski J, Ljungman G. Prevention of oral mucositis with cryotherapy in children undergoing hematopoietic stem cell transplantations-a feasibility study and randomized controlled trial. Support Care Cancer. 2020 Oct;28(10):4869-4879. doi: 10.1007/s00520-019-05258-2. Epub 2020 Jan 28.