Determining the Prognostic Value of Continuous Intrathecal Infusion

NCT03523000 | Completed Phase 4 Results FDA Drug FDA Device

• 1 other identifier: 08-16-09
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study will be to determine the efficacy and the prognostic value of a continuous intrathecal prognostic infusion test in an in-hospital setting for selecting patients who would have better long term outcomes for treatment with intrathecal implantable devices. The investigators will compare the primary outcomes \[changes in pain intensity score (NRS), patient global impression of change (PGIC)\] before and after intrathecal infusion of an admixture of bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml versus normal saline. The study will include 36 patients with intractable chronic low back pain in the setting of lumbar post-laminectomy syndrome or vertebral compression fracture who failed conservative management and are considered candidates for IDDS. Prior to the implant, the patients will undergo an intrathecal prognostic infusion test with an externalized catheter. Baseline NRS pain scores will be assessed and documented on all patients upon admission to the preoperative area. An intrathecal catheter will be placed in the outpatient procedure suite at the appropriate level for target dermatomes. The needle entry point will occur in the upper lumbar spine and catheter tip will be placed in the lower thoracic spine, under local anesthesia with the patient awake and with minimal or no sedation. The intrathecal infusion will be started using an external pump once patient is in the PACU. The research component is to perform the intrathecal test with normal saline (inactive placebo solution) in addition to a test with fentanyl and bupivacaine (active solution). Patients will be randomly assigned to either Group I (continuous infusion of bupivacaine and fentanyl followed by saline) or Group II (continuous infusion of saline followed by bupivacaine and fentanyl). In PACU, patients will be started on an infusion rate of 0.5 ml/hr and titrated to pain relief greater than 50% of baseline or up to 0.8-1.0 ml/hr within 6-8 hrs after start of the infusion. A clinician blinded to the treatment arm will assess NRS and PGIC on the patients after approximately 12 hours. Assessment will include changes in pain intensity score at rest and upon ambulating or performing maneuvers that normally elicit patient's low back pain. A 4-6-hour washout period will be allotted with infusion of preservative-free normal saline at a rate of 0.2 ml/hr, after which the physician will document a return of the NRS to baseline before switching therapies.

Conditions

Lumbar Post-Laminectomy Syndrome; Chronic Low Back Pain; Vertebral Compression Fracture; Failed Back Surgery Syndrome

Keywords

intractable chronic low back pain; lumbar post-laminectomy syndrome; vertebral compression fracture; intrathecal drug delivery system

Outcome Measures

Primary Outcomes (2)

• Change in Numerical Rating Scale Pain Scores (NRS) With Activity

  Numerical Rating Scale is an 11-point pain scale whereby 0 signifies no pain and 10 the worse pain ever

  Comparing change in NRS from baseline (Day 1) to: end of intrathecal infusion of solution 1 (Day 2), end of intrathecal infusion of solution 2 (Day 3)

• Change in Numerical Rating Scale Pain Scores (NRS) at Rest

  Numerical Rating Scale is an 11-point pain scale whereby 0 signifies no pain and 10 the worse pain ever

  Comparing change in NRS from baseline (Day 1) to: end of intrathecal infusion of solution 1 (Day 2), end of intrathecal infusion of solution 2 (Day 3)

Secondary Outcomes (7)

• Change in Oswestry Disability Score (ODI)

  Comparing change in ODI from baseline (Day 1) to: end of intrathecal infusion of solution 2 (Day 3)

• Change in painDETECT Total

  Comparing change in PainDETECT from baseline (Day 1) to: end of intrathecal infusion of solution 2 (Day 3)

• Change in painDETECT Final

  Comparing change in PainDETECT from baseline (Day 1) to: end of intrathecal infusion of solution 2 (Day 3)

• Change in Patient Global Impression of Change (PGIC)

  Comparing change in PGIC from end of intrathecal infusion of solution 1 (Day 2), to end of intrathecal infusion of solution 2 (Day 3)

• Treatment Satisfaction Questionnaire (TSQ)

  Up to one year

Study Arms (2)

Active Solution followed by Inactive Placebo Solution

ACTIVE COMPARATOR

Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml 6 hour washout followed by Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline

Other: Continuous intrathecal prognostic infusion test; Drug: Bupivacaine; Drug: Fentanyl; Drug: Placebo; Device: Intrathecal Drug Delivery System (IDDS)

Inactive Placebo Solution followed by Active Solution

PLACEBO COMPARATOR

Continuous intrathecal prognostic infusion test of inactive placebo solution: preservative-free normal saline 6 hour washout followed by Continuous intrathecal prognostic infusion test of active solution: intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml

Other: Continuous intrathecal prognostic infusion test; Drug: Bupivacaine; Drug: Fentanyl; Drug: Placebo; Device: Intrathecal Drug Delivery System (IDDS)

Interventions

Continuous intrathecal prognostic infusion test OTHER

The patient is infused with solution through the percutaneous intrathecal catheter at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Active Solution followed by Inactive Placebo Solution; Inactive Placebo Solution followed by Active Solution

Bupivacaine DRUG

Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Active Solution followed by Inactive Placebo Solution; Inactive Placebo Solution followed by Active Solution

Fentanyl DRUG

Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml continuous infusion at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Active Solution followed by Inactive Placebo Solution; Inactive Placebo Solution followed by Active Solution

Placebo DRUG

Intrathecal infusion of normal saline at a rate of 0.5-1.0 ml/hr for approximately 14-18 hours

Active Solution followed by Inactive Placebo Solution; Inactive Placebo Solution followed by Active Solution

Intrathecal Drug Delivery System (IDDS) DEVICE

40-mL IDDS containing a solution of fentanyl 50 mcg/mL with bupivacaine 30 mg/mL

Active Solution followed by Inactive Placebo Solution; Inactive Placebo Solution followed by Active Solution

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previous lumbar or thoracic spine surgery or lower thoracic/lumbar vertebral compression fracture
• Intractable pain of trunk (more than limbs)
• Patient who passed psychological evaluations as part of the usual clinical care prior to consideration of IDDS and are stable with current pain condition and medications
• Failed more conservative management.

You may not qualify if:

• Untreated coagulopathy or infection.
• Immune compromised state precluding having an implant.
• Allergic reactions to bupivacaine or fentanyl.
• Pregnancy
• Patients using more than 30 mg oral equivalents of morphine daily or who are unable to wean down below that dosage for more than 4 weeks before the prognostic intrathecal infusion test.
• Neurological deficits characterized as weakness in lower extremities with evidence of nerve damage
• Patients with cognitive disorders who would not be able to provide meaningful outcome responses

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (8)

• Hayek SM, Deer TR, Pope JE, Panchal SJ, Patel VB. Intrathecal therapy for cancer and non-cancer pain. Pain Physician. 2011 May-Jun;14(3):219-48.

  PMID: 21587327 BACKGROUND

• Deer TR, Prager J, Levy R, Rathmell J, Buchser E, Burton A, Caraway D, Cousins M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs MS, Kim P, Kumar K, Leong M, Liem L, McDowell GC 2nd, Panchal S, Rauck R, Saulino M, Sitzman BT, Staats P, Stanton-Hicks M, Stearns L, Wallace M, Willis KD, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus Conference 2012: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012 Sep-Oct;15(5):436-64; discussion 464-6. doi: 10.1111/j.1525-1403.2012.00476.x. Epub 2012 Jul 2.

  PMID: 22748024 BACKGROUND

• Dominguez E, Sahinler B, Bassam D, Day M, Lou L, Racz G, Raj P. Predictive value of intrathecal narcotic trials for long-term therapy with implantable drug administration systems in chronic non-cancer pain patients. Pain Pract. 2002 Dec;2(4):315-25. doi: 10.1046/j.1533-2500.2002.02040.x.

  PMID: 17156039 BACKGROUND

• Hamza M, Doleys D, Wells M, Weisbein J, Hoff J, Martin M, Soteropoulos C, Barreto J, Deschner S, Ketchum J. Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain. Pain Med. 2012 Oct;13(10):1304-13. doi: 10.1111/j.1526-4637.2012.01451.x. Epub 2012 Jul 30.

  PMID: 22845187 BACKGROUND

• Deer TR, Prager J, Levy R, Burton A, Buchser E, Caraway D, Cousins M, De Andres J, Diwan S, Erdek M, Grigsby E, Huntoon M, Jacobs M, Kim P, Kumar K, Leong M, Liem L, McDowell G, Panchal SJ, Rauck R, Saulino M, Staats P, Stanton-Hicks M, Stearns L, Sitzman BT, Wallace M, Willis KD, Witt W, Yaksh T, Mekhail N. Polyanalgesic Consensus Conference--2012: recommendations on trialing for intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel. Neuromodulation. 2012 Sep-Oct;15(5):420-35; discussion 435. doi: 10.1111/j.1525-1403.2012.00450.x. Epub 2012 Apr 11.

  PMID: 22494357 BACKGROUND

• Hayek SM, Veizi E, Hanes M. Intrathecal Hydromorphone and Bupivacaine Combination Therapy for Post-Laminectomy Syndrome Optimized with Patient-Activated Bolus Device. Pain Med. 2016 Mar;17(3):561-571. doi: 10.1093/pm/pnv021. Epub 2015 Dec 14.

  PMID: 26814257 BACKGROUND

• Veizi IE, Hayek SM, Narouze S, Pope JE, Mekhail N. Combination of intrathecal opioids with bupivacaine attenuates opioid dose escalation in chronic noncancer pain patients. Pain Med. 2011 Oct;12(10):1481-9. doi: 10.1111/j.1526-4637.2011.01232.x. Epub 2011 Sep 21.

  PMID: 21943351 BACKGROUND

• Hayek SM, Jones BA, Veizi E, Tran TQ, DeLozier SJ. Efficacy of Continuous Intrathecal Infusion Trialing with a Mixture of Fentanyl and Bupivacaine in Chronic Low Back Pain Patients. Pain Med. 2023 Jul 5;24(7):796-808. doi: 10.1093/pm/pnac195.

  PMID: 36515491 DERIVED

MeSH Terms

Conditions

post laminectomy syndrome; Failed Back Surgery Syndrome

Interventions

Bupivacaine; Fentanyl

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Salim Hayek
• Organization: University Hospitals Cleveland Medical Center

salim.hayek@uhhospitals.org

216-844-2685

Study Officials

• Salim Hayek, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The drugs will be delivered by the pharmacy to a blinded physician and labeled as Intrathecal solution 1 and Intrathecal solution 2 to be administered sequentially, separated by a 4-6-hr infusion of preservative-free saline. The content of Intrathecal solution 1 and 2 will be unknown to all investigators and participants in the study with the exception of the investigational pharmacy. The order of the Intrathecal solution (1 or 2) will be determined by pharmacy using a computer generated random sequence allocation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Anesthesiology/Chief, Division of Pain Medicine

Model Details: Patients who are considered candidates for intrathecal pump implant fulfilling the inclusion/exclusion criteria and who elect to participate in the study will be randomly assigned to two groups: Group A tested with continuous infusion of intrathecal bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for 14-18 hours followed by a trial with normal saline for another 14-18 hours; separated by a 4-6-hr infusion of preservative-free saline. Group B tested with intrathecal normal saline for 14-18 hours followed by intrathecal Bupivacaine 0.625 mg/ml and fentanyl 1 mcg/ml for another 14-18 hours; separated by a 4-6-hr infusion of preservative-free saline.

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: May 14, 2018
• Study Start: October 18, 2017
• Primary Completion: October 12, 2021
• Study Completion: October 12, 2021
• Last Updated: January 12, 2023
• Results First Posted: January 12, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)