Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial

Abstract

Cryoprevention (CP) using ice (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM). However, the use of IC may cause adverse reactions and requires water of safe quality to minimize risk of serious infections. This randomized, blinded, parallel group, phase 3 trial was conducted in five Scandinavian centers. Eligible patients were diagnosed with multiple myeloma or lymphoma, scheduled to receive conditioning with high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (ASCT). Patients were assigned to cooling with IC or a novel intraoral cooling device (ICD). The primary outcome was the highest OM score during the study period, expressed as peak value on the Oral Mucositis Assessment Scale (OMAS-total). When the entire study population (n = 172) was analyzed for peak OMAS-total, the two cooling methods were equally effective. However, when the lymphoma group was analyzed separately, the ICD significantly reduced the peak OMAS-total score to a greater extent compared to IC (x̄ ± SD; 1.77 ± 1.59 vs. 3.08 ± 1.50; p = 0.047). Combined with existing evidence, the results of the present trial confirm that CP is an effective method to prevent OM. ClinicalTrials.gov. NCT03203733.

Conflict of interest statement

BT, GL, KGL, and M Jädersten have no conflicts of interest to disclose. JW, AS, AM, and DEP report personal fees from BrainCool AB. RH reports personal fees from BrainCool AB, The National Swedish Beneficiary Authority (Government), and from EMA (European Medical Agency). FS reports personal fees from Amgen, Takeda, Skylite DX, and from Novartis, grants and personal fees from Celgene/BMS, Janssen, Oncopeptides and Sanofi, and grants from GSK. M Jontell reports consultation fee from Braincool AB and grants from Braincool AB.

© 2021. The Author(s).

Figures

Fig. 1. Flow diagram.

In total, ten patients (n = 10) dropped out of the enrolled study sample (n = 182; IC = 92; ICD = 90) related to the primary outcome (i) [n = 172; IC = 88; ICD = 84]. Two patients (n = 2; 1 in each intervention arm) did not continue the study due to fatal outcome related to disease progression. Eight patients (n = 8; 3 in the IC group and 5 in the ICD group) withdrew their consent to participate in the study. For the secondary outcome tolerability (ii–a) [n = 167; IC = 87; ICD = 80], 15 (n = 15; 5 in the IC group and 10 in the ICD group) patients were not able to pursue the assessment; for the secondary outcome patient-reported oral pain (ii–b) [n = 145; IC = 76; ICD = 69], 37 (n = 37; 16 in the IC group and 21 in the ICD group) did not submit the completed forms. IC, ice chips; ICD, intraoral cooling device.

Fig. 2. Peak OMAS-total.

Peak OMAS–total (mean) for the total population, myeloma group, and the lymphoma group following cooling with ice chips (ICs) or the intraoral cooling device (ICD).

Fig. 3. Kaplan-Meier diagram.

Number of patients at risk of severe oral mucositis, defined as peak OMAS–total ≥ 3 (%), following conditioning chemotherapy.

Fig. 4. Percentage of patients reporting discomfort after cooling with ice chips (ICs) or the intraoral cooling device (ICD).

Data are shown for the total population (n = 167: IC = 14/87; ICD = 4/80), myeloma group (n = 144: IC = 12/76; ICD = 3/68), and the lymphoma group (n = 23: IC = 2/11; ICD = 1/12).