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Safety and Efficacy Study of Hydromorphone Hydrochloride by Intrathecal Administration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Supportive Care
Condition Management of Chronic Pain
Interventions Drug: Hydromorphone Hydrochloride
Device: Programmable Implantable pump
Enrollment 153
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only)
Hide Arm/Group Description

Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Enrolled but Not Randomized, dropped out during Open Label phase. Open Label treatment only of their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Period Title: Open Label Phase
Started [1] 41 40 72
Completed 41 40 0
Not Completed 0 0 72
Reason Not Completed
Withdrawal by Subject             0             0             5
Adverse Event             0             0             8
Non-compliance With Study Drug             0             0             3
Investigator Decision             0             0             1
Sponsor Decision             0             0             2
Protocol Violation             0             0             1
Changes In The Subject's Condition Render The Subject Unacceptable For Further Treatment             0             0             1
Inadequate Pain Control             0             0             37
Other, Specify in text field in database             0             0             14
[1]
The purpose of the 12-week Open Label Phase of the trial is to titrate subjects to an optimal dose of hydromorphone hydrochloride and demonstrate the ability to maintain adequate pain relief in subjects requiring intrathecal opioid therapy.
Period Title: Randomized Phase
Started [1] 41 40 0
Completed 38 34 0
Not Completed 3 6 0
Reason Not Completed
Adverse Event             0             1             0
Lost to Follow-up             1             0             0
Inadequate Pain Control             1             2             0
Other, Specify text field in database             1             3             0
[1]
At the end of the Open Label Phase (ie, the 12 week chronic dosing period), subjects who meet criteria for randomization will be assigned to either remain at their current dose of hydromorphone hydrochloride or to have their dose titrated downward (control group) in a blinded fashion.
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only) Total
Hide Arm/Group Description

Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump

Enrolled but Not Randomized, dropped out during Open Label phase. Open Label treatment only of their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Total of all reporting groups
Overall Number of Baseline Participants 41 40 72 153
Hide Baseline Analysis Population Description
All Enrolled Subjects
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 40 participants 72 participants 153 participants
53.6  (11.5) 54.8  (8.3) 57.1  (9.7) 55.6  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 72 participants 153 participants
Female
27
  65.9%
25
  62.5%
40
  55.6%
92
  60.1%
Male
14
  34.1%
15
  37.5%
32
  44.4%
61
  39.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 72 participants 153 participants
Hispanic or Latino
1
   2.4%
2
   5.0%
3
   4.2%
6
   3.9%
Not Hispanic or Latino
40
  97.6%
38
  95.0%
69
  95.8%
147
  96.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 72 participants 153 participants
American Indian or Alaska Native
0
   0.0%
1
   2.5%
0
   0.0%
1
   0.7%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   7.3%
3
   7.5%
2
   2.8%
8
   5.2%
White
38
  92.7%
36
  90.0%
70
  97.2%
144
  94.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 41 participants 40 participants 72 participants 153 participants
41 40 72 153
1.Primary Outcome
Title Proportion of Subjects Who Are Treatment Failures During the Double-blind Randomized Withdrawal Period
Hide Description

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.

Time Frame 5 weeks [Baseline (Day 84) to Day 119 Visit]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized Subjects
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Measure Type: Count of Participants
Unit of Measure: Participants
18
  43.9%
24
  60.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments Superiority of intrathecal hydromorphone hydrochloride as compared to a control arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.147
Comments [Not Specified]
Method Chi-squared
Comments Pearson's chi-square test
2.Secondary Outcome
Title Brief Pain Inventory (BPI): Pain Severity, "Worst"
Hide Description '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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119 Visit]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Error)
Unit of Measure: score on a scale
5.62  (0.42) 6.62  (0.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments

P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.

Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).

Note: Baseline for this analysis is the Day 84 visit.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0342
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Brief Pain Inventory (BPI): Pain Severity "Average"
Hide Description '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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Error)
Unit of Measure: score on a scale
4.09  (0.34) 4.78  (0.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments

P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.

Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).

Note: Baseline for this analysis is the Day 84 visit.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1642
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Brief Pain Inventory (BPI): Pain Severity Summary Measure
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Error)
Unit of Measure: score on scale, mean of 4 assessments
4.19  (0.35) 5.24  (0.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments

P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.

Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).

Note: Baseline for this analysis is the Day 84 visit.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0160
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA, with randomization group as the factor and initial parameter value as covariate.
5.Secondary Outcome
Title Brief Pain Inventory: Interference With Function Summary Measure
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Error)
Unit of Measure: Mean of Pain interference with daily fun
3.76  (0.44) 5.54  (0.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments

P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.

Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).

Note: Baseline for this analysis is the Day 84 visit.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA, with randomization group as the factor and initial parameter value as covariate.
6.Secondary Outcome
Title Short-Form McGill Pain Questionnaire (SF-MPQ): Summary Score
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Error)
Unit of Measure: score on a scale, summed across 15 quest
11.05  (1.53) 16.95  (1.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments

P-value by ANCOVA, with randomization group as the factor and initial parameter value as covariate.

Note: For subjects with missing endpoint on Day 119, value is imputed using the Last Observation Carried Forward (LOCF).

Note: Baseline for this analysis is the Day 84 visit.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0088
Comments ANCOVA, with randomization group as the factor and initial parameter value as covariate.
Method ANCOVA
Comments [Not Specified]
7.Secondary Outcome
Title Time to Rescue Medication After Randomization (Days)
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: days
28.85  (6.32) 24.35  (9.67)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments Log-rank test for Kaplan-Meier Estimate of Time to Rescue (days).
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Patient Global Impression of Change (PGIC)
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119 / Treatment Failure]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.95  (1.70) 3.73  (2.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments P-value by the Cochran-Mantel-Haenszel mean score test (using equally spaced scores).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0335
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
9.Secondary Outcome
Title Oral Opioid Supplement Consumption
Hide Description 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.
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Mean (Standard Deviation)
Unit of Measure: milligrams (mg)
6916.88  (14102.91) 1732.84  (5984.53)
10.Secondary Outcome
Title Time to Rescue - Rescue Medication Given
Hide Description Number of subjects with rescue medication given
Time Frame 5 Weeks [Baseline (Day 84) to Day 119]
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat - Randomized
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Hide Arm/Group Description:

Subjects on hydromorphone hydrochloride for the duration of therapy.

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Hydromorphone Hydrochloride/Control Titrated Downward

Hydromorphone Hydrochloride: Opioid for chronic pain

Programmable Implantable pump: Programmable Implantable pump delivering intrathecal hydromorphone

Overall Number of Participants Analyzed 41 40
Measure Type: Count of Participants
Unit of Measure: Participants
16
  39.0%
27
  67.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Hydromorphone Hydrochloride (Randomized/Double-Blind), Hydromorphone Hydrochloride Titrated Downward/Control (Randomized/Double-Blind)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Pearson's chi-square test
Statistical Test of Hypothesis P-Value 0.010
Comments Pearson's chi-square test
Method Chi-squared
Comments [Not Specified]
Time Frame 24 Weeks
Adverse Event Reporting Description Includes all subjects who have study medication loaded into their intrathecal pump (ie, any exposure to hydromorphone hydrochloride).
 
Arm/Group Title Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only) All Subjects
Hide Arm/Group Description

Subjects stay on their current dose of Hydromorphone Hydrochloride administered via intrathecal (IT) pump; depending on the subject's starting dose on hydromorphone hydrochloride, either a 2 mg/mL or 10 mg/mL formulation may be used.

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Subjects have their current dose of Hydromorphone Hydrochloride dose titrated downward; administered via Intrathecal pump

Hydromorphone Hydrochloride: Opioid for chronic pain

Device: Programmable Implantable pump delivering intrathecal hydromorphone hydrochloride

Enrolled but not randomized [Entered Open Label Phase includes visits from Day 1 until date of randomization (Day 84)] Total serious adverse events from Day 1 through end of study
All-Cause Mortality
Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/41 (0.00%)   0/40 (0.00%)   0/72 (0.00%)   0/153 (0.00%) 
Hide Serious Adverse Events
Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/41 (4.88%)   6/40 (15.00%)   9/72 (12.50%)   17/153 (11.11%) 
Cardiac disorders         
Angina Unstable  1  0/41 (0.00%)  1/40 (2.50%)  0/72 (0.00%)  1/153 (0.65%) 
Gastrointestinal disorders         
Oesophageal Achalasia  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
General disorders         
Drug Withdrawal Syndrome  1  0/41 (0.00%)  2/40 (5.00%)  0/72 (0.00%)  2/153 (1.31%) 
Drug Intolerance  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Non-Cardiac Chest Pain  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Hepatobiliary disorders         
Cholecystitis  1  0/41 (0.00%)  1/40 (2.50%)  1/72 (1.39%)  2/153 (1.31%) 
Infections and infestations         
Clostridium Difficile Colitis  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Implant Site Abscess  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Implant Site Cellulitis  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Incision Site Infection  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Pneumonia  1  0/41 (0.00%)  1/40 (2.50%)  0/72 (0.00%)  1/153 (0.65%) 
Injury, poisoning and procedural complications         
Craniocerebral Injury  1  1/41 (2.44%)  0/40 (0.00%)  1/72 (1.39%)  2/153 (1.31%) 
Cervical Vertebral Fracture  1  1/41 (2.44%)  0/40 (0.00%)  0/72 (0.00%)  1/153 (0.65%) 
Seroma  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Musculoskeletal and connective tissue disorders         
Osteoarthritis  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Nervous system disorders         
Akathisia  1  0/41 (0.00%)  1/40 (2.50%)  0/72 (0.00%)  1/153 (0.65%) 
Basal Ganglia Stroke  1  1/41 (2.44%)  0/40 (0.00%)  0/72 (0.00%)  1/153 (0.65%) 
Headache  1  0/41 (0.00%)  1/40 (2.50%)  0/72 (0.00%)  1/153 (0.65%) 
Hypoaesthesia  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Paraesthesia  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Radiculopathy  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
Syncope  1  0/41 (0.00%)  0/40 (0.00%)  1/72 (1.39%)  1/153 (0.65%) 
1
Term from vocabulary, MedDRA (12.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Hydromorphone Hydrochloride (Randomized/Double-Blind) Hydromorphone Titrated Downward/Control (Randomized/Double-Blind) Not Randomized (Open Label Only) All Subjects
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/41 (85.37%)   36/40 (90.00%)   56/72 (77.78%)   127/153 (83.01%) 
Gastrointestinal disorders         
Nausea  1  12/41 (29.27%)  15/40 (37.50%)  8/72 (11.11%)  35/153 (22.88%) 
Diarrhoea  1  4/41 (9.76%)  10/40 (25.00%)  3/72 (4.17%)  17/153 (11.11%) 
Vomiting  1  3/41 (7.32%)  7/40 (17.50%)  2/72 (2.78%)  12/153 (7.84%) 
Constipation  1  2/41 (4.88%)  5/40 (12.50%)  1/72 (1.39%)  8/153 (5.23%) 
Abdominal Discomfort  1  1/41 (2.44%)  2/40 (5.00%)  0/72 (0.00%)  3/153 (1.96%) 
Gastrooesophageal Reflux Disease  1  0/41 (0.00%)  2/40 (5.00%)  1/72 (1.39%)  3/153 (1.96%) 
General disorders         
Drug Withdrawal Syndrome  1  3/41 (7.32%)  11/40 (27.50%)  8/72 (11.11%)  22/153 (14.38%) 
Pain  1  3/41 (7.32%)  5/40 (12.50%)  3/72 (4.17%)  11/153 (7.19%) 
Oedema Peripheral  1  3/41 (7.32%)  1/40 (2.50%)  3/72 (4.17%)  7/153 (4.58%) 
Chills  1  1/41 (2.44%)  2/40 (5.00%)  1/72 (1.39%)  4/153 (2.61%) 
Oedema  1  2/41 (4.88%)  2/40 (5.00%)  0/72 (0.00%)  4/153 (2.61%) 
Chest Pain  1  0/41 (0.00%)  2/40 (5.00%)  1/72 (1.39%)  3/153 (1.96%) 
Asthenia  1  0/41 (0.00%)  2/40 (5.00%)  0/72 (0.00%)  2/153 (1.31%) 
Infections and infestations         
Bronchitis  1  3/41 (7.32%)  2/40 (5.00%)  3/72 (4.17%)  8/153 (5.23%) 
Gastroenteritis Viral  1  1/41 (2.44%)  3/40 (7.50%)  2/72 (2.78%)  6/153 (3.92%) 
Sinusitis  1  3/41 (7.32%)  1/40 (2.50%)  2/72 (2.78%)  6/153 (3.92%) 
Upper Respiratory Tract Infection  1  3/41 (7.32%)  1/40 (2.50%)  0/72 (0.00%)  4/153 (2.61%) 
Injury, poisoning and procedural complications         
Contusion  1  2/41 (4.88%)  2/40 (5.00%)  2/72 (2.78%)  6/153 (3.92%) 
Fall  1  1/41 (2.44%)  3/40 (7.50%)  0/72 (0.00%)  4/153 (2.61%) 
Joint Injury  1  3/41 (7.32%)  0/40 (0.00%)  0/72 (0.00%)  3/153 (1.96%) 
Thermal Burn  1  0/41 (0.00%)  2/40 (5.00%)  0/72 (0.00%)  2/153 (1.31%) 
Metabolism and nutrition disorders         
Decreased Appetite  1  1/41 (2.44%)  3/40 (7.50%)  0/72 (0.00%)  4/153 (2.61%) 
Musculoskeletal and connective tissue disorders         
Back Pain  1  5/41 (12.20%)  9/40 (22.50%)  7/72 (9.72%)  21/153 (13.73%) 
Arthralgia  1  2/41 (4.88%)  3/40 (7.50%)  6/72 (8.33%)  11/153 (7.19%) 
Pain In Extremity  1  0/41 (0.00%)  5/40 (12.50%)  5/72 (6.94%)  10/153 (6.54%) 
Neck Pain  1  2/41 (4.88%)  2/40 (5.00%)  4/72 (5.56%)  8/153 (5.23%) 
Musculoskeletal Pain  1  3/41 (7.32%)  2/40 (5.00%)  2/72 (2.78%)  7/153 (4.58%) 
Muscle Spasms  1  1/41 (2.44%)  2/40 (5.00%)  1/72 (1.39%)  4/153 (2.61%) 
Sacroiliitis  1  0/41 (0.00%)  2/40 (5.00%)  0/72 (0.00%)  2/153 (1.31%) 
Nervous system disorders         
Headache  1  4/41 (9.76%)  4/40 (10.00%)  6/72 (8.33%)  14/153 (9.15%) 
Somnolence  1  2/41 (4.88%)  1/40 (2.50%)  4/72 (5.56%)  7/153 (4.58%) 
Sciatica  1  0/41 (0.00%)  2/40 (5.00%)  3/72 (4.17%)  5/153 (3.27%) 
Lethargy  1  1/41 (2.44%)  2/40 (5.00%)  0/72 (0.00%)  3/153 (1.96%) 
Hypoaesthesia  1  0/41 (0.00%)  2/40 (5.00%)  0/72 (0.00%)  2/153 (1.31%) 
Psychiatric disorders         
Anxiety  1  1/41 (2.44%)  4/40 (10.00%)  2/72 (2.78%)  7/153 (4.58%) 
Skin and subcutaneous tissue disorders         
Hyperhidrosis  1  3/41 (7.32%)  3/40 (7.50%)  2/72 (2.78%)  8/153 (5.23%) 
Vascular disorders         
Hypertension  1  1/41 (2.44%)  3/40 (7.50%)  2/72 (2.78%)  6/153 (3.92%) 
1
Term from vocabulary, MedDRA (12.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Heather Kapushoc, Sr. Biostatistician
Organization: CTI Clinical Trial and Consulting Services
Phone: 571-315-2574
EMail: hkapushoc@ctifacts.com
Layout table for additonal information
Responsible Party: Piramal Critical Care, Ltd.
ClinicalTrials.gov Identifier: NCT01709721    
Other Study ID Numbers: CNS-HYD201US
First Submitted: August 24, 2012
First Posted: October 18, 2012
Results First Submitted: July 22, 2021
Results First Posted: August 17, 2021
Last Update Posted: August 17, 2021