Cryotherapy for Prevention of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation

A Randomized Controlled Trial of Cryotherapy for Prevention and Reduction of Severity of Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation.

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.

Study Overview

• Status: Completed
• Conditions: Pain; Infection; Oral Mucositis; Nutrition Aspect of Cancer
• Intervention / Treatment: Other: Cryotherapy

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

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, SE-41685
    • Pediatric Oncology Department, Queen Silvia Childrens´ Hospital
  • Lund, Sweden, SE-22185
    • Departent of Pediatric Oncology, Lund University Hospital
  • Stockholm, Sweden, SE-14186
    • Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Hudding
  • Stockholm, Sweden, Se-14186
    • Department of pediatrics B78, Karolinska University Hospital
  • Uppsala, Sweden, SE-75185
    • Department of Hematology, Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryotherapy; Cryotherapy during conditioning treatment with chemotherapy prior to HSCT	Other: Cryotherapy; Cryotherapy with ice-chips, ice cream or ice water is given during conditioning treatment with chemotherapy prior to HSCT.
No Intervention: Control; Standard oral Care. No Cryotherapy during conditioning treatment prior to HSCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucositis grade - WHO Oral Toxicity Scale	WHO-Oral toxicity scale Grade 0 - No mucositis Grade 1 - Erythema and/or soreness Grade 2 - Erythema and/or ulcers. Can eat solid food. Grade 3 - Erythema and/or Ulcers. No solid food but can ingest liquids. Grade 4 - Oral alimentation not possible.	Daily until engraftment, an expected average of 20 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mucositis grade - Children´s International Mucositis Evaluation Scale (ChiMES)	Daily evaluation by child and parent.	Daily until engraftment, an expected average of 20 days.
Pain - Childrens Hospital Eastern Ontario Pain Scale (CHEOPS)	Daily assessment by nurse	Daily until Engraftment an expected average of 20 days.
Mouth Pain	Mouth Pain measured with Numerical Rating scale(NRS)for children >7 years and parents and Facial Pain Scale(FPS) for children < 7 years	Daily until Engraftment an expected average of 20 days
Emotional and Psychological status	Beck youth inventories for depression and anxiety	Daily until engraftment, an expected average of 20 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Days with, and dose of morphine-equivalent opioids	During hospitalization in connection with HSCT, an expected average of 25 days
Duration of parenteral nutrition	Days with Total Parenteral Nutrition	During hospitalization in connection with HSCT, an expected average of 25 days
Weight Loss	Weight Loss in kilograms from admission to date of engraftment	During hospitalization in connection with HSCT, an expected average of 25 days
Duration of Antibiotic treatment	Days with antibiotics	During hospitalization in connection with HSCT, an expected average of 25 days
Duration of febrile neutropenia	Days with fever >38.0 degrees	Until engraftment, an expected average of 20 days
Duration of Hospitalisation	Counted from day 0 until discharge either home or to region hospital.	During hospitalization in connection with HSCT, an expected average of 25 days
C reactive protein	Level of p-CRP in comparison to grade of mucositis	During hospitalization in connection with HSCT, an expected average of 25 days
S-Albumin	In correlation to grade of Oral Mucositis	During hospitalization in connection with HSCT, an expected average of 25 days

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: The Swedish Childhood Cancer Foundation
• Investigators: Study Director: Gustaf Ljungman, MD, PhD, Uppsala University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 8, 2013
• First Posted (Estimate): February 12, 2013

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Children; Cryotherapy; Hematopoietic Stem Cell Transplantation; Oral Mucositis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis
• Other Study ID Numbers: UU-OM-01