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

• Sponsor: St. Jude Children's Research Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00187135
• Collaborator: (none)
• Enrollment: 168
• Location: 1
• Arms: 3
• Duration (Months): 77
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Bone Marrow Disease; Pain	Drug: Fentanyl; Drug: EMLA; Drug: L.M.X4; Drug: Propofol	Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Fentanyl-Propofol-EMLA or L.M.X4™ Technique for Bone Marrow Aspiration in Pediatric Patients - A Phase III Study
• Study Start Date: Mar 1, 2002
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Fentanyl-1mcg/kg in 3 ml of Normal Saline	Drug: Fentanyl; Fentanyl - 1 mcg/kg in 3 ml normal saline Fentanyl - 0.5 mcg/kg in 3 ml normal saline; Drug: EMLA; 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.; Drug: L.M.X4; 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.; Drug: Propofol; 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.
Active Comparator: 2 Fentanyl - 0.5 mcg/kg in 3 ml normal saline	Drug: Fentanyl; Fentanyl - 1 mcg/kg in 3 ml normal saline Fentanyl - 0.5 mcg/kg in 3 ml normal saline; Drug: EMLA; 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.; Drug: L.M.X4; 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.; Drug: Propofol; 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.
Placebo Comparator: 3 normal saline	Drug: EMLA; 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.; Drug: L.M.X4; 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.; Drug: Propofol; 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.

Outcome Measures

Primary Outcome Measures

1. Pain(Yes/No) [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.]

   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.

2. Pain (Yes/No) [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.]

   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.

Secondary Outcome Measures

1. 20% or Greater Change in Heart Rate [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.]

   Measurements of 20% change in Heart Rate (yes/no) taken during recovery after surgery.

2. 20% or Greater Change in Respiratory Rate [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.]

   Measurements of 20% change in respiratory rate(yes/no) taken during recovery after surgery.

3. 20% or Greater Change in Blood Pressure [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.]

   Measurements of 20% change in blood pressure(yes/no) taken during recovery after surgery.

4. Movement [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 (yes/no) measured during recovery after surgery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105

Sponsors and Collaborators

• St. Jude Children's Research Hospital

Investigators

• Principal Investigator: Doralina L. Anghelescu, M.D., St. Jude Children's Research Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• St. Jude Children's Research Hospital

Publications

None provided.

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT00187135
• Other Study ID Numbers: PFE
• First Posted: Sep 16, 2005
• Last Update Posted: Apr 4, 2017
• Last Verified: Mar 1, 2010

• Keywords provided by St. Jude Children's Research Hospital: Pain Management; Bone Marrow Aspiration
• Additional relevant MeSH terms: Bone Marrow Diseases; Fentanyl; Propofol

Study Results

Participant Flow

Recruitment Details	A total of 168 participants were enrolled between March, 2002 and August, 2007.
Pre-assignment Detail	168 participants were enrolled and were expected to receive 3 Bone Marrow Aspirations/Lumbar Puncture Intrathecal Chemotherapy procedures; 6 patients withdrew (eg: medical withdrawal, withdrawal of consent and other). 162 were randomized, of which 77 completed all 3 treatments.

Arm/Group Title	Fentanyl 0.5 / Placebo / Fentanyl 1	Fentanyl 0.5 /Fentanyl 1 / Placebo	Placebo / Fentanyl 0.5 /Fentanyl 1	Placebo /Fentanyl 1 / Fentanyl 0.5	Fentanyl 1 / Fentanyl 0.5 / Placebo	Fentanyl 1 / Placebo /Fentanyl 0.5
Arm/Group Description	Participants assigned to receive Fentanyl 0.5 micrograms per kilogram (mcg/kg) during their first visit, Placebo (Pl)during their second visit, and Fentanyl 1 micrograms per kilogram at the final visit.	Participants assigned to receive Fentanyl 0.5 micrograms per kilogram (mcg/kg) during their first visit, Fentanyl 1 micrograms per kilogram (mcg/kg) during their second visit, and Placebo at the final visit.	Participants assigned to receive Placebo during their first visit, Fentanyl 0.5 micrograms per kilogram (mcg/kg) during their second visit, and Fentanyl 1 micrograms per kilogram (mcg/kg) at the final visit.	Participants assigned to receive Placebo during their first visit, Fentanyl 1 micrograms per kilogram (mcg/kg) during their second visit, and Fentanyl 0.5 micrograms per kilogram (mcg/kg) at the final visit.	Participants assigned to receive Fentanyl 1 micrograms per kilogram (mcg/kg) during their first visit Fentanyl 0.5 micrograms per kilogram (mcg/kg) during their second visit, and Placebo at the final visit.	Participants assigned to receive Fentanyl 1 micrograms per kilogram (mcg/kg) during their first visit Placebo during their second visit, and Fentanyl 0.5 micrograms per kilogram (mcg/kg) at the final visit.
Period Title: Visit One
STARTED	30	28	25	26	25	28
COMPLETED	26	27	25	26	25	26
NOT COMPLETED	4	1	0	0	0	2
Period Title: Visit One
STARTED	26	27	25	26	25	26
COMPLETED	21	24	23	18	19	18
NOT COMPLETED	5	3	2	8	6	8
Period Title: Visit One
STARTED	21	24	23	18	19	18
COMPLETED	14	17	14	9	11	12
NOT COMPLETED	7	7	9	9	8	6

Baseline Characteristics

Arm/Group Title	Fentanyl 0.5/Placebo/Fentanyl 1	Fentanyl 0.5/Fentanyl 1/Placebo	Placebo/Fentanyl 0.5/Fentanyl 1	Placebo/Fentanyl 1/Fentanyl 0.5	Fentanyl 1/Fentanyl 0.5/Placebo	Fentanyl 1/Placebo/Fentanyl 0.5	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	30	28	25	26	25	28	162
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.4 (4.3)	7.2 (4.5)	7.6 (4.8)	7.1 (4.1)	7.3 (4.7)	7.1 (4.4)	7.1 (4.4)
Sex: Female, Male (Count of Participants)
Female	15 50%	11 39.3%	12 48%	10 38.5%	9 36%	13 46.4%	70 43.2%
Male	15 50%	17 60.7%	13 52%	16 61.5%	16 64%	15 53.6%	92 56.8%

Outcome Measures

1. Primary Outcome

Title	Pain(Yes/No)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Participants in this analysis are a subset of the 162 participants randomized since not all completed 3 visits on study. If a participant completed at least Visit 2 and received each of the 2 treatments compared they are included. Treatment on each visit was randomized; therefore these numbers cannot be derived directly from the participant flow.

Arm/Group Title	Fentanyl 1mcg/kg vs Placebo	Fentanyl 0.5mcg/kg vs Placebo
Arm/Group Description	Patients who completed treatment with Fentanyl 1 mcg/kg and placebo.	Patients who completed treatment with Fentanyl 0.5 mcg/kg and placebo.
Measure Participants	71	79
Pain with Fentanyl and pain with Placebo	0 0%	6 21.4%
Pain with Fentanyl and no-pain with Placebo	7 23.3%	8 28.6%
No-pain with Fentanyl pain with Placebo	10 33.3%	5 17.9%
No-pain with Fentanyl no-pain with Placebo	54 180%	60 214.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 0.5mcg/kg vs Placebo
	Comments	The study was designed to achieve statistical power of 80% for this comparison. Due to the early termination of the study, the sample size needed to ensure adequate statistical power for this comparison was not obtained.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments	To adjust for multiple comparisons, p-values less than 0.0167 are considered statistically significant.
	Method	McNemar
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo
	Comments	The study was designed to achieve statistical power of 80% for this comparison. The sample size needed to ensure adequate statistical power for this comparison was obtained.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments	To adjust for multiple comparisons, p-values less than 0.0167 are considered statistically significant.
	Method	McNemar
	Comments

2. Primary Outcome

Title	Pain (Yes/No)
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Participants in this analysis are a subset of the 162 participants randomized since not all completed 3 visits on study. If a participant completed at least Visit 2 and received each of the 2 treatments compared they are included. Treatment on each visit was randomized; therefore these numbers cannot be derived directly from the participant flow.

Arm/Group Title	Fentanyl 0.5mcg/kg vs Fentanyl 1mcg/kg
Arm/Group Description	Patients who completed treatment with Fentanyl 0.5 mcg/kg and Fentanyl 1mcg/kg.
Measure Participants	74
Pain on Fentanyl (1), Pain on Fentanyl (0.5)	2 6.7%
Pain on Fentanyl (1) No-pain on Fentanyl (0.5)	3 10%
No-Pain on Fentanyl (1), Pain on Fentanyl (0.5)	5 16.7%
No-Pain on Fentanyl (1), No-Pain on Fentanyl (0.5)	64 213.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo
	Comments	The study was designed to achieve statistical power of 80% for this comparison. Due to the early termination of the study, the sample size needed to ensure adequate statistical power for this comparison was not obtained.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments	To adjust for multiple comparisons, p-values less than 0.0167 are considered statistically significant.
	Method	McNemar
	Comments

3. Secondary Outcome

Title	20% or Greater Change in Heart Rate
Description	Measurements of 20% change in Heart Rate (yes/no) taken during recovery after surgery.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Due to study termination, not all Participants completed three planned visits. 107 of the 162 participants enrolled on study received treatment with Fentanyl 0.5 mcg/kg. 104 of the 162 participants enrolled on study received treatment with Fentanyl 1mcg/kg. 105 of the 162 participants enrolled on study received treatment with Placebo.

Arm/Group Title	Fentanyl 0.5mcg/kg	Fentanyl 1mcg/kg	Placebo
Arm/Group Description	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 0.5 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 1mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Placebo are included in this arm. Participants were included regardless of whether they received other treatments.
Measure Participants	107	104	105
Yes	7 23.3%	6 21.4%	8 32%
No	100 333.3%	98 350%	97 388%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo, Fentanyl 0.5mcg/kg vs Placebo, Placebo
	Comments	The generalized estimation equation (GEE) approach by Liang and Zeger was used to model the effects of 20% change in heart rate (HR) on pain (Y/N) while controlling for treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.87
	Comments
	Method	GEE Model
	Comments

4. Secondary Outcome

Title	20% or Greater Change in Respiratory Rate
Description	Measurements of 20% change in respiratory rate(yes/no) taken during recovery after surgery.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Due to study termination, not all Participants completed three planned visits. 107 of the 162 participants enrolled on study received treatment with Fentanyl 0.5 mcg/kg. 104 of the 162 participants enrolled on study received treatment with Fentanyl 1mcg/kg. 105 of the 162 participants enrolled on study received treatment with Placebo.

Arm/Group Title	Fentanyl 0.5mcg/kg	Fentanyl 1mcg/kg	Placebo
Arm/Group Description	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 0.5 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 1mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Placebo are included in this arm. Participants were included regardless of whether they received other treatments.
Measure Participants	107	104	105
Yes	21 70%	20 71.4%	24 96%
No	86 286.7%	84 300%	81 324%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo, Fentanyl 0.5mcg/kg vs Placebo, Placebo
	Comments	The generalized estimation equation (GEE) approach by Liang and Zeger was used to model the effects of 20% change in respiratory rate (RR) on pain (Y/N) while controlling for treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	GEE Model
	Comments

5. Secondary Outcome

Title	20% or Greater Change in Blood Pressure
Description	Measurements of 20% change in blood pressure(yes/no) taken during recovery after surgery.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Due to study termination, not all participants completed three planned visits. 107 of the 162 participants enrolled on study received treatment with Fentanyl 0.5 mcg/kg. 104 of the 162 participants enrolled on study received treatment with Fentanyl 1mcg/kg. 105 of the 162 participants enrolled on study received treatment with Placebo.

Arm/Group Title	Fentanyl 0.5mcg/kg	Fentanyl 1mcg/kg	Placebo
Arm/Group Description	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 0.5 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 1mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Placebo are included in this arm.
Measure Participants	107	104	105
Yes	12 40%	10 35.7%	14 56%
No	95 316.7%	94 335.7%	91 364%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo, Fentanyl 0.5mcg/kg vs Placebo, Placebo
	Comments	The generalized estimation equation (GEE) approach by Liang and Zeger was used to model the effects of 20% change in blood presure (BP) on pain (Y/N) while controlling for treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	GEE Model
	Comments

6. Secondary Outcome

Title	Movement
Description	Movement (yes/no) measured during recovery after surgery.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Due to study termination, not all participants completed three planned visits. 107 of the 162 participants enrolled on study received treatment with Fentanyl 0.5 mcg/kg. 104 of the 162 participants enrolled on study received treatment with Fentanyl 1mcg/kg. 105 of the 162 participants enrolled on study received treatment with Placebo.

Arm/Group Title	Fentanyl 0.5mcg/kg	Fentanyl 1mcg/kg	Placebo
Arm/Group Description	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 0.5 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 1mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Placebo are included in this arm.
Measure Participants	107	104	105
Yes	57 190%	45 160.7%	58 232%
No	50 166.7%	59 210.7%	47 188%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fentanyl 1mcg/kg vs Placebo, Fentanyl 0.5mcg/kg vs Placebo, Placebo
	Comments	The generalized estimation equation (GEE) approach by Liang and Zeger was used to model the effects of motion (Y/N)on pain (Y/N) while controlling for treatment.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	GEE Model
	Comments

Adverse Events

Time Frame	Adverse events were assessed from the time of procedure up to 7 days post procedure
Adverse Event Reporting Description	Four participants died during the study period.All 4 deaths were due to the primary disease or complications of the disease process.None of the deaths occurred within 7 days of that patient's procedure for which data was collected, and therefore is unrelated to the study treatment.
Arm/Group Title	Fentanyl 0.5mcg/kg		Fentanyl 1mcg/kg		Placebo
Arm/Group Description	Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 0.5 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.		Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Fentanyl 1.0 mcg/kg are included in this arm. Participants were included regardless of whether they received other treatments.		Due to study termination, not all Participants completed three planned visits. Participants who completed at least one treatment with Placebo are included in this arm. Participants were included regardless of whether they received other treatments.
All Cause Mortality
	Fentanyl 0.5mcg/kg		Fentanyl 1mcg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fentanyl 0.5mcg/kg		Fentanyl 1mcg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/104 (0%)		0/105 (0%)
Other (Not Including Serious) Adverse Events
	Fentanyl 0.5mcg/kg		Fentanyl 1mcg/kg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/104 (0%)		0/105 (0%)

Limitations/Caveats

All 162 participants were expected to receive three treatments. Not all participants received all three treatments. Therefore, analysis required the identification of subsets of treated participants. The trial terminated early due to slow accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.