Trial Outcomes & Findings for Patient Controlled Intrathecal Analgesia With Bupivacaine for Chronic Low Back Pain (NCT NCT02886286)

NCT ID: NCT02886286

Last Updated: 2022-03-24

Results Overview

Patients will be provided with a diary to record pain scores just before a PTM bolus and the lowest pain score within half an hour after a PTM bolus. Numerical Rating Pain Scale (NRS): scale from 0-10 0 = no pain 10 = worst imaginable pain

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 17 participants
• Primary outcome timeframe: Before self-administered bolus using Patient Therapy Manager device (PTM) and within 30 minutes of PTM bolus
• Results posted on: 2022-03-24

Participant Flow

Participant milestones

Measure	Bupivacaine + Opioid First, Then Opioid Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients received Bupivacaine + Opioid first for 7 days. Patients were crossed over at day 8 to receive Opioid only. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid First, Then Bupivacaine + Opioid Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only first for 7 days. Patients were crossed over at day 8 to receive Bupivacaine + Opioid. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Overall Study STARTED	8	9
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Bupivacaine + Opioid First, Then Opioid Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients received Bupivacaine + Opioid first for 7 days. Patients were crossed over at day 8 to receive Opioid only. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid First, Then Bupivacaine + Opioid Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only first for 7 days. Patients were crossed over at day 8 to receive Bupivacaine + Opioid. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Overall Study pump motor stall	0	1

Baseline Characteristics

Patient Controlled Intrathecal Analgesia With Bupivacaine for Chronic Low Back Pain

Baseline characteristics by cohort

Measure	Bupivacaine + Opioid n=8 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain	Opioid n=8 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age, Continuous	63.125 years STANDARD_DEVIATION 8.96 • n=5 Participants	63.75 years STANDARD_DEVIATION 10.8 • n=7 Participants	63.43 years STANDARD_DEVIATION 9.93 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Before self-administered bolus using Patient Therapy Manager device (PTM) and within 30 minutes of PTM bolus

Population: All participants who received each intervention were included in the analysis.

Patients will be provided with a diary to record pain scores just before a PTM bolus and the lowest pain score within half an hour after a PTM bolus.

Numerical Rating Pain Scale (NRS): scale from 0-10 0 = no pain 10 = worst imaginable pain

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in the Numerical Rating Pain Scale (NRS)	1.87 units on a scale Standard Deviation 1.4	1.81 units on a scale Standard Deviation 1.47

SECONDARY outcome

Timeframe: Day 0, 7, 14, score at day 7 or day 14 reported

Population: All participants who received each intervention were included in the analysis.

Oswestry Disability Index (ODI): calculated as a percentage based on scores from 0-5 in 10 categories (pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, travelling). 0 signifies no pain interference while 5 signifies maximum possible pain interference in the 10 categories. Scores from 0-5 for 10 categories are added and divided by total possible score (50) X 100 to give percentage.

Interpretation of percentage scores:

0 - 20% minimal disability 21-40% moderate disability 41-60% severe disability 61-80% crippled 81-100% either bed bound or patient is exaggerating symptoms

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in Oswestry Disability Index (ODI)	.88 units on a scale Standard Deviation 9.4	2.67 units on a scale Standard Deviation 9.02

SECONDARY outcome

Timeframe: Day 0, 7, 14, score at day 7 or day 14 reported

Population: All participants who received each intervention were included in the analysis.

Patient Global Impression of Change (PGIC): reflects patient's belief about the efficacy of treatment

1. = very much improved

2. = much improved

3. = minimally improved

4. = no change

5. = worse

6. = much worse

7. = very much worse

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in Patient Global Impression of Change (PGIC)	-0.06 units on a scale Standard Deviation 2.11	1.25 units on a scale Standard Deviation 1.81

SECONDARY outcome

Timeframe: Day 0, 7, 14, score at day 7 or day 14 reported

Population: All participants who received each intervention were included in the analysis.

painDETECT is a nine-item questionnaire that consists of seven sensory symptom items for pain that are graded from 0= never to 5= strongly, one temporal item on pain-course pattern graded -1 to +1, and one spatial item on pain radiation graded 0 for no radiation or +2 for radiating pain. A total score that ranges from -1 to 38 can be calculated from the nine items, with higher scores indicating higher levels of pain.

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in painDETECT	0.69 units on a scale Standard Deviation 2.96	0.25 units on a scale Standard Deviation 4.75

SECONDARY outcome

Timeframe: Day 0, 7, 14, score at day 7 or day 14 reported

Population: All participants who received each intervention were included in the analysis.

Average Weekly Numeric Pain Rating Score (NRS) over the past week

Numerical Rating Pain Scale (NRS): scale from 0-10 0 = no pain 10 = worst imaginable pain

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in Average Weekly Numeric Pain Rating Score (NRS)	-0.47 units on a scale Standard Deviation 1.59	-0.38 units on a scale Standard Deviation 1.69

SECONDARY outcome

Timeframe: Day 0, 7, 14, score at day 7 or day 14 reported

Population: All participants who received each intervention were included in the analysis.

A 5-point qualitative Likert scale was used to report measures of patient satisfaction (i.e., not satisfied at all, not satisfied, somewhat, satisfied, very satisfied). To quantify satisfaction, these responses were transformed to a scale of 0-4, with higher numbers representing greater levels of satisfaction.

Outcome measures

Measure	Bupivacaine + Opioid n=16 Participants Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 Participants Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Change From Baseline in Treatment Satisfaction	2.36 units on a scale Standard Deviation 1.22	1.94 units on a scale Standard Deviation 1.18

Adverse Events

Bupivacaine + Opioid

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Opioid

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Bupivacaine + Opioid n=16 participants at risk Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. Bupivacaine: Patient-activated intrathecal bolus for incident pain Opioid: Patient-activated intrathecal bolus for incident pain Patients who received Bupivacaine + Opioid for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.	Opioid n=16 participants at risk Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be \>2 and \<10. Opioid: Patient-activated intrathecal bolus for incident pain Patients received Opioid only for 7 days, either in the first 7 days or last 7 days of the study. Bolus delivery was locked out after each medication change for one to two days. Data were collected on days 4-7 and days 11-14.
Nervous system disorders headache	18.8% 3/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
Nervous system disorders numbness/tingling	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	12.5% 2/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
Nervous system disorders nausea	12.5% 2/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
General disorders fatigue	0.00% 0/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
Psychiatric disorders anxiety	0.00% 0/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
Skin and subcutaneous tissue disorders skin irritation	0.00% 0/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events
Renal and urinary disorders urinary hesitancy	0.00% 0/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events	6.2% 1/16 • 2 weeks Removing the local anesthetic from the intrathecal solution does not cause withdrawal, mortality or serious adverse events

Additional Information

Salim M. Hayek, MD, PhD

University Hospitals Cleveland Medical Center

Phone: 2168442685

Email: salim.hayek@uhhospitals.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place