Study of Fentanyl-Propofol-EMLA of L.M.X4 Technique for Bone Marrow Aspiration

Study Overview
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Brief Summary
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St. Jude Children's Research Hospital is studying the best ways to prevent pain during and after procedures such as bone marrow aspiration and lumbar puncture with intrathecal (in the spinal fluid) chemotherapy. Researchers will study the effectiveness of combining anesthetics (medicines that help people sleep) and analgesics (medicines that relieve pain). Researchers believe that a combination of fentanyl (analgesic) and propofol (anesthetic), along with applying the skin-numbing-cream EMLA or L.M.X4™ on the area where the procedure is performed, will provide better pain control. Each patient enrolled on this study will have three different anesthetic combinations for three different procedures, in order to determine which combination worked best for each child.

Detailed Description
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The study focusses on the following primary aims: To compare 0.5 mg/kg versus 1.0 mg/kg of fentanyl to control pain in patients who have a BMT/LPIT procedure in the context of propofol anesthesia and topical anesthesia with EMLA or L•M•X 4™cream (or when necessary, lidocaine for injection). To compare placebo versus fentanyl (0.5 mg/kg or 1.0 mg/kg) in these same patients. The first BMT/LPIT for which patients receive any fentanyl will be used in this comparison. The study focusses on the following secondary aims: To determine which dose regimen ensures best conditions to perform bone marrow aspiration (lack of motion) and maintains hemodynamic and respiratory stability as indicators of adequate levels of analgesia during bone marrow aspiration. To evaluate the safety and complications for each dose regimen.

Official Title
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Fentanyl-Propofol-EMLA or L.M.X4™ Technique for Bone Marrow Aspiration in Pediatric Patients - A Phase III Study

Conditions
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Bone Marrow Disease, Pain

Intervention / Treatment
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* Drug: Fentanyl
* Drug: EMLA
* Drug: L.M.X4
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing bone marrow aspiration (unilateral), with lumbar puncture and intrathecal chemotherapy. Age 2 to 17 years ASA I-III Patients with acute lymphoblastic leukemia or lymphoblastic lymphoma in remission or on the day of anticipated remission procedures occurring at the end of remission induction. Patients must have three anticipated bone marrow aspirates and lumbar punctures with intrathecal chemotherapy remaining in their treatment Exclusion Criteria: Newly diagnosed patients Patients with low platelet count (less than 50000) Patients undergoing bone marrow biopsy in addition to bone marrow aspiration Age less than 2 years or over 17 years ASA IV-V Patients taking opioid medication for pre-existent pain for more than 2 weeks at the time of the procedure Neurological impairment that would increase susceptibility to opioids (Down's syndrome) Clinical contraindications for general anesthesia (large mediastinal mass) or specific use of propofol, Fentanyl, EMLA, L•M•X 4™ or Lidocaine for injection

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Fentanyl-1mcg/kg in 3 ml of Normal Saline | Drug: Fentanyl<br>* Fentanyl - 1 mcg/kg in 3 ml normal saline Fentanyl - 0.5 mcg/kg in 3 ml normal saline<br>Drug: EMLA<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). EMLA application has to be over at least 60 minutes and not to exceed 5 hours.<br>Drug: L.M.X4<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). In order to optimize transdermal anesthesia LMX4 application has to be over at least 30 minutes.<br>Drug: Propofol<br>* Propofol - 1 mg/kg increments every 30 seconds-1minute until loss of consciousness is indicated by lack of response to verbal command and loss of eyelid reflex.<br>|
| Active Comparator: 2<br>Fentanyl - 0.5 mcg/kg in 3 ml normal saline | Drug: Fentanyl<br>* Fentanyl - 1 mcg/kg in 3 ml normal saline Fentanyl - 0.5 mcg/kg in 3 ml normal saline<br>Drug: EMLA<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). EMLA application has to be over at least 60 minutes and not to exceed 5 hours.<br>Drug: L.M.X4<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). In order to optimize transdermal anesthesia LMX4 application has to be over at least 30 minutes.<br>Drug: Propofol<br>* Propofol - 1 mg/kg increments every 30 seconds-1minute until loss of consciousness is indicated by lack of response to verbal command and loss of eyelid reflex.<br>|
| Placebo Comparator: 3<br>normal saline | Drug: EMLA<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). EMLA application has to be over at least 60 minutes and not to exceed 5 hours.<br>Drug: L.M.X4<br>* All patients will have EMLA or LMX4 cream applied at the anticipated site of the bone marrow aspiration to ensure topical anesthesia, and will receive a total intravenous anesthetic technique (TIVA). In order to optimize transdermal anesthesia LMX4 application has to be over at least 30 minutes.<br>Drug: Propofol<br>* Propofol - 1 mg/kg increments every 30 seconds-1minute until loss of consciousness is indicated by lack of response to verbal command and loss of eyelid reflex.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain(Yes/No) | During the sedation recovery period, pain was measured by one of three validated pediatric scales. Scales were applied according to the developmental ability of the participant: Numerical Pain Scale, FACES pain scale, and FLACC pain scale (a score based on behaviors observed: face, legs, activity, cry, and consolability). All three scales are scored from 0 - 10 units on a scale, and are interchangeable for comparison purposes. Any score >0 was coded pain, and score of 0 was coded no pain, yielding one score for each participant's procedure. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 
| Pain (Yes/No) | During the sedation recovery period, pain was measured by one of three validated pediatric scales. Scales were applied according to the developmental ability of the participant: Numerical Pain Scale, FACES pain scale, and FLACC pain scale (a score based on behaviors observed: face, legs, activity, cry, and consolability). All three scales are scored from 0 - 10 units on a scale, and are interchangeable for comparison purposes. Any score >0 was coded pain, and score of 0 was coded no pain, yielding one score for each participant's procedure. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 20% or Greater Change in Heart Rate | Measurements of 20% change in Heart Rate (yes/no) taken during recovery after surgery. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 
| 20% or Greater Change in Respiratory Rate | Measurements of 20% change in respiratory rate(yes/no) taken during recovery after surgery. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 
| 20% or Greater Change in Blood Pressure | Measurements of 20% change in blood pressure(yes/no) taken during recovery after surgery. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 
| Movement | Movement (yes/no) measured during recovery after surgery. | The participant was monitored from the end of the procedure until sedation recovery, which lasted a maximum of 65 min. Discharge from the recovery area was determined by hospital standards of care. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain Management, Bone Marrow Aspiration