A Randomized Single Center Trial to Determine the Efficacy of Methadone as a First Line Agent in the Reduction and Treatment of Pain in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Reduction of pain score
研究概览
简要总结
Mucositis is a normal side effect of stem cell transplant which happens as a result of chemotherapy being given prior to a new donor cell infusion (bone marrow transplant). The chemotherapy will kill cancer cells, but good cells, such as those in the mouth, are killed too. The mouth cells going away causes the areas in the mouth to be blistered, irritated, sore, and extremely painful. Pain medication (usually morphine or hydromorphone if allergic to morphine) are given when oral blisters are seen or felt by patient in patient's mouth. However, one pain medication given through a vein in the patient may or may not be effective and providers are often challenged with providing good pain control while waiting for the new donor cells to grow, which will then heal the mouth. This is a period of waiting that is 6-8 weeks.
The investigators know that methadone, a second pain medication, may decrease pain in a different way than morphine. This is because methadone works in a different way in the brain than morphine. By giving these pain medicines together, the hope of the study is to show decreased pain while waiting for new cells to grow.
The goal of this clinical trial is to hope to learn whether adding methadone (second pain medication) to the current pain medication which is morphine alone (all patients will receive this pain medication) will help reduce the pain experience of participant. Current treatment of morphine alone is sometimes not entirely effective and so any improvement of pain while waiting for new cells to grow is one of the goals of this study. If methadone is effective in decreasing pain, then patients may benefit in the future from using these two medications up front when getting a transplant.
Participant in this study between 6-18 years of age and is needing a stem cell transplant for a disease that can potentially be cured by transplantation.
Participant in this study is receiving chemotherapy and/or radiation conditioning that can cause mucositis. Participants are being asked to participate in this study because participants meet criteria to receive methadone that may or may not reduce pain experience versus just being given morphine alone, which is what all patients are given when the participants have mucositis.
The main goal of the study is to see if less opioid (pain medication) when methadone is added in comparison to participant who uses PCA only. The investigators also want to learn if patient's overall function is improved if given methadone. Another goal would be to see the number of TPN days the participant received and if the participant who was given methadone began to eat sooner. Other smaller goals include learning about side effects of methadone, and if the hospital stay is less for those who receive the study medication.
This medication will be given at Children's Medical Center of Dallas while participant is admitted for the stem cell transplant. There is no sponsor that is funding the study and this drug will be given free of charge in exchange for participation in the study
详细描述
Given high reports of pain while despite receiving PCA during transplant, our current management of mucositis induced pain is suboptimal. In a study of children receiving transplantation, pain was a main concern for this cohort during and after transplantation. The investigators propose to conduct this study to determine if methadone used as a primary analgesic in patients with mucositis can improve the current standard of care which will be demonstrated by improved pain scores, maintenance of functionality, and recovery during and following HSCT. This study will be a single blind randomized controlled design. Patients will be randomly assigned by permuted block randomization in groups of eight. Patient will be randomly assigned to receive either basal/PCA of one opioid (control) in the first arm OR PCA plus methadone where methadone will be used as basal long-acting medication (experimental).
Study subjects will be children who are undergoing an autologous or allogeneic stem cell transplant receiving a myeloablative regimen and meet all inclusion criteria. This unique population is being studied as it is a controlled setting where the PI can anticipate pain in >90% of the patients following ablation, the number of patients who experience mucositis after receiving ablative conditioning. The study will only be conducted in the inpatient stem cell transplant setting and no follow up should be necessary when these subjects are discharged from the hospital after transplant.
The following goals of the study are as follows:
- Will the concomitant administration of intravenous administered methadone with on demand opioid PCA improve pain score numbers in the PCA/methadone arm (experimental) in comparison to a continuous infusion PCA with demand opioid arm (control, standard of care)?
- Will the administration of methadone with increased individualized titration result in a reduction of 25% in total morphine milligram equivalents (MME) in experimental versus control arm?
- Will the methadone experimental arm increase functionality during transplantation period?
- Will those receiving methadone have reduced TPN days during hospital stay as compared to control arm?
- Will the child resumes oral intake more rapidly compared to control arm?
- The investigators also want to describe adverse events and incidence associated with methadone when administered in combination with morphine or hydromorphone, specifically QTc prolongation that has been documented with study medication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Care Provider)
盲法说明
Parent would be masked as well
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All subjects admitted will receive a myeloablative conditioning regimen followed by autologous or allogeneic bone marrow transplant during transplant admission. Conditioning may include chemotherapy, radiation, or a combination of both methods to be determined by primary attending transplant physician. Diagnoses will include but not limited to those with liquid tumors, solid tumors, hematological/congenital blood disorders, or severe combined immunodeficiency syndromes.
- •Subjects must be 6-18 years of age and demonstrate understanding of PCA use or have a parent available for PCA by proxy, meaning parent can push the button for the patient. Patient maximum age is 18 years old. PCA proxy in compliance with Pain Assessment and Management policy per institution.
- •Performance status: Karnofsky/Lansky >50% prior to receiving conditioning.
- •Be cognitively able to utilize and understand patient-controlled analgesia (PCA).
- •Informed consent will be obtained from all participants or their parents or guardians, assent will be obtained from children ages 10-17 years of age per institutional policy.
排除标准
- •QT prolongation prior to receiving myeloablative conditioning as evidenced by QTc being >450 for both girls and boys prior to starting methadone.
- •Medical history of QT prolongation, VF, or VT.
- •Patients on chronic pain medications on admission or have received more than 30 days of continuous opioids over the past month.
- •Patients receiving a non-myeloablative regimen or no conditioning.
- •Neurological or psychiatric condition that could confound reliable assessment of pain and sedation (non-verbal, global delay).
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to morphine or other agents used in study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
- •History of opioid misuse disorder OR opioid risk assessment tool score >8.
研究组 & 干预措施
Group A: Control Arm (n = 30)
Pt will receive: PCA opioid will include morphine OR hydromorphone (if patient has a sensitivity or is unable to tolerate or allergic to morphine). This is the exclusive medication/opioid in this arm. The starting doses will be as follows:
- Starting dose for basal infusion of morphine is 0.02 mg/kg/hour up to a maximum of 50 kg.
- Starting PCA dose for morphine is 0.02 mg/kg every 15 minutes for a lockout of 0.1 mg/kg up to a maximum of 50 kg or ideal body weight (PCA starting dose should be no more than 1 mg/push and no more than 5 mg/hour lockout).
- Starting dose for basal infusion of hydromorphone is 0.003 mg/kg/hour up to a maximum of 50 kg IBW.
- Starting PCA dose for hydromorphone is 0.003 mg/kg every 15 minutes for an hourly maximum lockout of 0.012 mg/kg up to a maximum of 50 kg (PCA start
- PCA medications may be titrated up or down by 20-50% each day for desired analgesic effect with improved pain score, continue to engraftment or when medicine is no longer needed.
干预措施: PCA Alone (SOC) (Drug)
Group B: Study or Experimental Arm (n = 30)
The second arm will be methadone therapy that is scheduled to be given every 8 hours in addition to an on demand PCA. On demand PCA dosing will be the same as control arm but with NO basal/continuous rate. Intravenous methadone will be replacing basal infusion and serve as basal drug in place of continuous medication.
- Starting dose for intravenous methadone is 0.1 mg/kg IV Q8hr up to a maximum of 50 kg. Singular starting methadone will be maximum of 5 mg.
- Methadone may be increased by 20-50% every 48 hours due to half-life of medication. Reduction in analgesia will need to be monitored daily following a change. However, additional methadone increase should not occur until 48 hours have passed to allow for steady state of new dose to take effect. Reduction of methadone dosing by 20-50% can be made anytime per discretion of provider or if concerned about an adverse effect from the methadone.
This will continue until engraftment or until medicine is no longer needed.
干预措施: PCA plus methadone (Experimental) (Drug)
结局指标
主要结局
Reduction of pain score
时间窗: Daily after completion of conditioning (day +7 to day +14) through discharge (approximately day +60)
The purpose of the study is to compare methadone versus standard of care at this center of morphine/hydromorphone PCA and see if methadone is superior to the standard of care as evidenced by reduction in pain scores during inpatient transplant. To determine whether concomitant administration of intravenous administered methadone with on demand opioid PCA will improve pain score numbers in the PCA/methadone arm by 25% in comparison to a continuous infusion PCA with demand opioid arm.
次要结局
- IMPROVEMENT OF FUNCTIONALITY as evidenced by higher functionality scores in experimental arm in comparison to control(Day 0 (stem cell infusion))
- REDUCTION OF OPIOID RECEIVED as evidenced by 25% reduction of MME in experimental arm in comparison to control arm(Daily after completion of conditioning (day +7 to day +14) through discharge (approximately day +60))
- REDUCED NUMBER OF DAYS ON PARENTERAL NUTRITION as evidenced by reduced number of TPN days in experimental arm in comparison to control(From enrollment (initiation of TPN- typically on day +1) to engraftment day AND date when able to take solid food again (day just prior to discharge-approx. day+50 to day+60))
- INCREASED RETURN TO ORAL LIQUID INTAKE as evidenced by more rapid return to tolerating clears in experimental group versus control(From enrollment (initiation of TPN- typically on day +1) to engraftment day AND date when able to take solid food again (day just prior to discharge-approx. day+50 to day+60))
- Adverse events(From first dose of methadone administered (day +1- day +7) until prior to discharge (approximately day +60))
研究者
James DeMasi
Nurse Practitioner - Anesthesiology and Pain Management
Children's Health