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Safety and Efficacy Study of Hydromorphone Hydrochloride by Intrathecal Administration

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ClinicalTrials.gov Identifier: NCT01709721
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : August 17, 2021
Last Update Posted : August 17, 2021
Sponsor:
Information provided by (Responsible Party):
Piramal Critical Care, Ltd.

Brief Summary:
The purpose of this study is to determine the safety and efficacy of hydromorphone hydrochloride by intrathecal administration using a programmable implantable pump.

Condition or disease Intervention/treatment Phase
Management of Chronic Pain Drug: Hydromorphone Hydrochloride Device: Programmable Implantable pump Phase 3

Detailed Description:
A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a Programmable Implantable Pump

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Official Title: A Controlled, Two-Arm, Parallel Group, Randomized Withdrawal Study to Assess the Safety and Efficacy of Hydromorphone Hydrochloride Delivered by Intrathecal Administration Using a Programmable Implantable Pump
Actual Study Start Date : February 2013
Actual Primary Completion Date : February 2018
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain

Arm Intervention/treatment
Experimental: Hydromorphone Hydrochloride (Randomized/Double-Blind)
Subjects on hydromorphone hydrochloride for the duration of therapy.
Drug: Hydromorphone Hydrochloride
Opioid for chronic pain
Other Names:
  • Hydromorphone
  • Opioid

Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone

Active Comparator: Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Subjects on hydromorphone hydrochloride titrated downward
Drug: Hydromorphone Hydrochloride
Opioid for chronic pain
Other Names:
  • Hydromorphone
  • Opioid

Device: Programmable Implantable pump
Programmable Implantable pump delivering intrathecal hydromorphone




Primary Outcome Measures :
  1. Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period [ Time Frame: 5 weeks [Baseline (Day 84) to Day 119 Visit] ]

    Treatment failure during the Randomized Phase is defined as at least one of the following: a) increase of >= 20mm VASPI vs. baseline over 5 days; b) intolerable pain that in investigator's opinion requires intervention; or c) pain-related interventions that violate protocol from Day 84 to Day 119.

    Note: Baseline pain for the randomized phase is defined as the average of the last 5 days with daily pain measurements while on an optimal intrathecal dose of Hydromorphone, between Days 77 and 83 of the open label dosing period.

    Note: A subject who does not have sufficient data for evaluation, drops out for any other reasons that are not listed above or who experiences withdrawal syndrome as identified by COWS > 12 during the randomized phase will not be classified as a treatment failure.

    Note: Analysis period is from beginning of randomization phase (Day 84) to end of study.



Secondary Outcome Measures :
  1. Brief Pain Inventory (BPI): Pain Severity, "Worst" [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119 Visit] ]
    'Worst' pain experienced in the past 24 hours. Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.

  2. Brief Pain Inventory (BPI): Pain Severity "Average" [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    'Average' pain experienced in the past 24 hours. The Brief Pain Inventory (BPI): Scale: 0 = No Pain, 10 = Pain as bad as you can imagine; a high score indicates a worse outcome.

  3. Brief Pain Inventory (BPI): Pain Severity Summary Measure [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    Pain severity will be evaluated by rating pain on a scale from 0 (no pain) to 10 (pain as bad as you can imagine) for the 'worst', 'least', and 'average' pain experienced in the past 24 hours, as well as, the pain experienced 'now'. In addition, a calculated mean pain severity score will be based on the sum of all 4 of the pain scores divided by 4. If any of the 4 questions are missing, then the calculated mean pain severity score will be considered missing. High values indicate worse outcome.

  4. Brief Pain Inventory: Interference With Function Summary Measure [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    Pain interference with daily functioning will be evaluated by rating interference on a scale from 0 (does not interfere) to 10 (completely interferes) for 'general activity', 'mood', 'walking ability', 'normal work', 'relation with other people', 'sleep', and 'enjoyment of life'. A calculated mean pain interference will be based on the sum of non-missing interference questions answered divided by the number of questions answered. The mean should be set to missing if fewer than 4 pain interference questions are answered. A high score is worse.

  5. Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    The SF-MPQ consists of a 15 item pain rating index. The severity of each item will be scored as None (0), Mild (1), Moderate (2), or Severe (3). The total SF-MPQ score is the sum of the severity scores for each item. The total score can range from 0 to 45; high score is worse.

  6. Time to Rescue Medication After Randomization (Days) [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    The number of days to rescue will be calculated by calculating the number of hours between the time of randomization and the time of rescue. The number of hours will then be divided by 24 to obtain the number of days.

  7. Patient Global Impression of Change (PGIC) [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure] ]
    The PGIC rating represents observed changes (if any) from the subject's Baseline Visit in activity limitations, symptoms, emotions, and overall quality of life, related to the subject's painful condition. Change is rated on a 7-point Likert-type scale from 1 (no change) through 7 (a great deal better). High score is better outcome.

  8. Oral Opioid Supplement Consumption [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    Total consumption (mg) = The total number of milligrams consumed of any oral opioid product from Day 84 (Baseline) through the end of study will be calculated for each subject.

  9. Time to Rescue - Rescue Medication Given [ Time Frame: 5 Weeks [Baseline (Day 84) to Day 119] ]
    Number of subjects with rescue medication given



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria to be included:

  1. Subject must be at least 18 years of age and no more than 75 years old.
  2. Clinically diagnosed with chronic pain for at least a 6-month period.
  3. Subject is presently on intrathecal pain medication and has a SynchroMed II Implantable pump or meets clinical criteria for implantation of a SynchroMed II Implantable pump. Subjects who are naïve to intrathecal therapy, may be enrolled 2-weeks after pump implantation.
  4. Subject agrees to sign a Pain Treatment Agreement (Narcotic Contract) limiting narcotic prescriptions to the study physician.
  5. Subject must be cognitively intact and, in the opinion of the investigator, capable of participation in the trial.
  6. Female subjects of child-bearing potential must agree to use a medically acceptable and effective double-barrier method of birth control.
  7. Subjects with existing SynchroMed II Implantable pumps and are reasonably expected to benefit from intrathecal opioid therapy only.
  8. Subjects who are capable of receiving an MRI with or without contrast or CT myelogram, if required by the study protocol.
  9. Provides written Ethics Committee approved informed consent.
  10. Willing to comply with all study procedures and requirements..

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded:

  1. Women who are pregnant or are breast-feeding
  2. Subjects who have participated in an investigational drug or device trial within 4 weeks prior to enrollment.
  3. Subject has any known or suspected allergy to hydromorphone or to the materials of the infusion pump or intrathecal catheter.
  4. Subject is scheduled for a pump or catheter replacement within 6 months of their enrollment into the trial.
  5. Subject has a history of dependence and abuse of opioids, stimulants, alcohol, or benzodiazepines, as defined by DSM-IV criteria, within the past year (physical dependence on prescribed opioid analgesics is allowed but abuse of opioids according to DSM-IV is not permitted, i.e. opioid addiction for recreational use).
  6. Subjects who show signs of active systemic infection.
  7. Subjects with a metastatic cancer to the spinal canal or a known central nervous system contraindication to intrathecal therapy.
  8. Subject has a condition requiring diathermy procedures.
  9. Subject has a life expectancy of less than 12 months.
  10. Subject cannot independently comprehend and participate in the required assessments, including responding to the VASPI, Short-form McGill Pain Questionnaire (SF-MPQ), Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), BPI and patient global impression of change (PGIC) measurement tools.
  11. Subject is not considered to be medically or psychologically appropriate for pump implantation.
  12. Subjects who are unable or unwilling to return to all of the required follow-up visits.
  13. Subjects with active implanted devices such as pacemakers, defibrillators, and cochlear implants or other medical device use, if in the opinion of the investigator the device would interfere with the ability to perform an MRI or CT myelogram.
  14. As a result of medical review and physical examination, the Investigator considers the subject unfit for the study.
  15. Pain located above the shoulders in the head or neck region (e.g. trigeminal neuralgia), central pain syndromes or any other condition in which it is judged to be unlikely that the subject would benefit from intrathecal administration of the drug product.
  16. Subjects who have previously been unresponsive to intrathecal hydromorphone therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01709721


Locations
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United States, North Carolina
The Center for Clinical Research
Winston-Salem, North Carolina, United States, 27103
Sponsors and Collaborators
Piramal Critical Care, Ltd.
Investigators
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Principal Investigator: Richard L Rauck, MD The Center for Clinical Research
  Study Documents (Full-Text)

Documents provided by Piramal Critical Care, Ltd.:
Study Protocol  [PDF] August 1, 2016
Statistical Analysis Plan  [PDF] February 4, 2019

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Responsible Party: Piramal Critical Care, Ltd.
ClinicalTrials.gov Identifier: NCT01709721    
Other Study ID Numbers: CNS-HYD201US
First Posted: October 18, 2012    Key Record Dates
Results First Posted: August 17, 2021
Last Update Posted: August 17, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Piramal Critical Care, Ltd.:
Hydromorphone
Hydromorphone Hydrochloride
Pain Management
Non-narcotic analgesics
Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations
Hydromorphone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents