Bone Marrow DiseasePhase 3NCT00187135

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

A Phase 3 study testing Fentanyl, EMLA and L.M.X4 in people with Bone Marrow Disease and Pain, run by St. Jude Children's Research Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 2 to 17 years
Conditions the study is for: Bone Marrow Disease, Pain
What is being tested?: Fentanyl, EMLA and L.M.X4
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 168 participants
Where: 1 siteUnited States
Study dates: Mar 2002to Aug 2008
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Bone Marrow Disease, Pain
Being tested: Fentanyl, EMLA, L.M.X4, Propofol
Keywords: Pain Management, Bone Marrow Aspiration
Medical subject headings: Bone Marrow Diseases, Pain, Agnosia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FentanylDrug
1. Fentanyl - 1 mcg/kg in 3 ml normal saline
2. Fentanyl - 0.5 mcg/kg in 3 ml normal saline
EMLADrug
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.
L.M.X4Drug
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.
PropofolDrug
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.

Study groups in NCT00187135
Study group	Role	What they receive
1	Active comparator	Fentanyl-1mcg/kg in 3 ml of Normal Saline Receives: Drug: Fentanyl; Drug: EMLA; Drug: L.M.X4; Drug: Propofol
2	Active comparator	Fentanyl - 0.5 mcg/kg in 3 ml normal saline Receives: Drug: Fentanyl; Drug: EMLA; Drug: L.M.X4; Drug: Propofol
3	Placebo comparator	normal saline Receives: Drug: EMLA; Drug: L.M.X4; Drug: Propofol

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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 outcomes (4)

20% or Greater Change in Heart Rate
Measurements of 20% change in Heart Rate (yes/no) taken during recovery after surgery.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2002Aug 2008

First posted16 Sep 2005 (estimated)
Study startMar 2002
Primary completionAug 2008
Study completionAug 2008

Why it stopped: The study was terminated due to slow accrual.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bone Marrow DiseaseStudies of the same condition, open and under way.
More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 168 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00187135
Sponsor's protocol ID: PFE
Status last verified: Mar 2010
First submitted: 12 Sep 2005
Last updated: 4 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bone Marrow Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Fentanyl-Propofol-EMLA or L.M.X4™ Technique for Bone Marrow Aspiration in Pediatric Patients - A Phase III Study
ClinicalTrials.gov ID: NCT00187135
Acronym / sponsor ID: PFE
Conditions: Bone Marrow Disease, Pain
Keywords: Pain Management, Bone Marrow Aspiration
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated due to slow accrual.
Enrolment: 168 participants (actual)
Lead sponsor: St. Jude Children's Research HospitalUniversity, hospital or other
Study start: Mar 2002
Primary completion: Aug 2008 (actual)
Study completion: Aug 2008 (actual)
First posted: 16 Sep 2005 (estimated)
Results: Posted 19 Mar 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

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

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
1	Active comparator	Drug: Fentanyl, Drug: EMLA, Drug: L.M.X4, Drug: PropofolFentanyl-1mcg/kg in 3 ml of Normal Saline
2	Active comparator	Drug: Fentanyl, Drug: EMLA, Drug: L.M.X4, Drug: PropofolFentanyl - 0.5 mcg/kg in 3 ml normal saline
3	Placebo comparator	Drug: EMLA, Drug: L.M.X4, Drug: Propofolnormal saline

Who may qualify

Ages: 2 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fentanyl1. Fentanyl - 1 mcg/kg in 3 ml normal saline 2. Fentanyl - 0.5 mcg/kg in 3 ml normal saline	Drug	1, 2
EMLAAll 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	1, 2, 3
L.M.X4All 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	1, 2, 3
PropofolPropofol - 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.	Drug	1, 2, 3

Primary outcome

Pain(Yes/No)
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.
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.
Pain (Yes/No)
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.
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.

4 secondary outcomes

20% or Greater Change in Heart Rate
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.
20% or Greater Change in Respiratory Rate
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.
20% or Greater Change in Blood Pressure
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.
Movement
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.

Results and safety

Results posted to the registry on 19 Mar 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fentanyl 0.5 / Placebo / Fentanyl 1	30	26
Fentanyl 0.5 /Fentanyl 1 / Placebo	28	27
Placebo / Fentanyl 0.5 /Fentanyl 1	25	25
Placebo /Fentanyl 1 / Fentanyl 0.5	26	26
Fentanyl 1 / Fentanyl 0.5 / Placebo	25	25
Fentanyl 1 / Placebo /Fentanyl 0.5	28	26

Primary outcome: Pain(Yes/No)

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.. Number. Unit: Participants

Measure	Fentanyl 1mcg/kg vs Placebo n = 71	Fentanyl 0.5mcg/kg vs Placebo n = 79
Pain with Fentanyl and pain with Placebo	0	6
Pain with Fentanyl and no-pain with Placebo	7	8
No-pain with Fentanyl pain with Placebo	10	5
No-pain with Fentanyl no-pain with Placebo	54	60

Fentanyl 0.5mcg/kg vs Placebo: p = 0.5, McNemar
Fentanyl 1mcg/kg vs Placebo: p = 0.5, McNemar

Population analysed: 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.

Primary outcome: Pain (Yes/No)

Measure	Fentanyl 0.5mcg/kg vs Fentanyl 1mcg/kg n = 74
Pain on Fentanyl (1), Pain on Fentanyl (0.5)	2
Pain on Fentanyl (1) No-pain on Fentanyl (0.5)	3
No-Pain on Fentanyl (1), Pain on Fentanyl (0.5)	5
No-Pain on Fentanyl (1), No-Pain on Fentanyl (0.5)	64

Fentanyl 0.5mcg/kg vs Fentanyl 1mcg/kg: p = 0.5, McNemar

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were assessed from the time of procedure up to 7 days post procedure. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fentanyl 0.5mcg/kg	0 of 107 (0%)	0 of 107 (0%)	Not reported
Fentanyl 1mcg/kg	0 of 104 (0%)	0 of 104 (0%)	Not reported
Placebo	0 of 105 (0%)	0 of 105 (0%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
St. Jude Children's Research HospitalLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Doralina L. Anghelescu, M.D. principal investigator

St. Jude Children's Research Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fentanyl, EMLA and L.M.X4 in people with Bone Marrow Disease and Pain, run by St. Jude Children's Research Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Mar 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pain(Yes/No) (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00187135.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.