Trial Information

Ketamine and Hydromorphone PCA Analgesia for Antineoplastic-Induced Pediatric Mucositis

The purpose of this observational pilot study is to evaluate the feasibility, efficacy and
optimum ratio of a compounded mixture of HM-K administered parenterally by PCA in pediatric
mucositis patients who have inadequate analgesia using conventional HM PCA.

An open-label study of 20 consecutive consenting/assenting subjects who meet the study
criteria will be conducted. All patients who are eligible for the study will be approached
for informed, written consent and subjects over age 7 will complete an assent form.

The subject will be examined by a pediatric oncology fellow/staff to determine the level of
clinical severity of the mucositis using the Oral Mucositis Assessment Scale (OMAS) and
World Health Organization Mucositis Scale.

A modified Colour Analogue Scale (mCAS) that was originally designed to evaluate pain
intensity will be used to evaluate the self-report symptoms. The subject will then receive
24 hours of therapy using a compounded HM-K PCA solution.

Initial PCA prescription for the Background and Bolus will be set at the existing settings
on the morning of recruitment as per the study entry criteria of minimum hourly use of 4
mcg/kg/hour of HM. The 1-hour Maximum will be set at 4 times the Background dose.

At 24 hours, the 24-hour HM and K consumption will be calculated. The subject will be
re-examined by a pediatric oncology fellow/staff to determine the level of clinical severity
of the mucositis and the self-report symptom evaluation questionnaire administered.
Conventional Therapy of HM PCA will be restarted and at 24 hours, both the mucositis
severity and the self-report symptom evaluation questionnaire administered. Descriptive
summaries of the demographic data will be provided. The 24-hour HM utilization will be
compared to the study entry-level utilization (24 hour period prior to recruitment). A 30%
reduction in opioid use will be considered clinically important.A Symptom Index of Start
Study Symptom Level - End Study Symptom Level / Start Study Symptom level will be calculated
for each symptom including pain intensity. An Index of greater than or equal to 0.5 will be
considered a positive outcome. Indexes at 0, 24 and 48 hours will be compared. A descriptive
summary of the incidence and treatment of opioid-induced side effects at 0, 24 and 48 hours
will be provided.

Ketamine Solution Concentrations

Solution 1 (low): HM 0.2 and K 0.2 mg/mL (1:1) - 20 mg/20 mg in 100 mL. Solution 2 (medium):
HM 0.2 and K 0.6 mg/mL (1:3) - 20 mg/60 mg in 100 mL. Solution 3 (high): HM 0.2 and K 1
mg/mL (1:5) - 20 mg/100 mg in 100 mL.

The starting solution will be Solution 2 in a minimum dose 4 mcg/kg/hour of hydromorphone
(HM) and 12 mcg/kg/hour of ketamine (K) (0.02 mL/kg/hour of solution.

"Add background": 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of solution)
may occur once as required after solution change criteria are met.

"Increase background": additional 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour
of solution).

Repeat "Increase background": 4 mcg/kg/hour of Hydromorphone equivalent (0.02 mL/kg/hour of
solution) may occur 3 hourly as required after solution change criteria are met.

"Decrease background": decrease by 4 mcg/kg/hour of Hydromorphone equivalent (0.02
mL/kg/hour of solution) may occur 3 hourly as required after solution change criteria are
met.

"Stop background": Background is stopped so that only bolus dose remains. May occur when
background has been reduced to 4 mcg/kg/hour of Hydromorphone for at least 3 hours or
exceessive ADEs.

"D/C background: Discontinue background HM and only bolus remains.

"Stop Study (SS)": Converting the PCA to conventional HM therapy with any adjuvants required
according to existing practice of Acute Pain Service. For compassionate reasons, if a
patient/family expresses a with to remain on STudy Therapy, this will be accepted.

Once patient has ADEs and requires Solution 1, they may not re-start solution 2 or 3.