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Phase 3 Completed N=410 Randomized Double-blind Treatment

A Research Study of an Investigational Drug ALO-02 (Oxycodone Hydrochloride and Naltrexone Hydrochloride) in Patients With Moderate to Severe Chronic Low Back Pain

Source: ClinicalTrials.gov NCT01571362 ↗
Enrolled (actual)
410
Serious AEs
1.5%
Results posted
Apr 2017
Primary outcomePrimary: Change in Weekly Average Electronic Diary (eDiary) Numeric Rating Scale -Pain (NRS-Pain) Score From Randomization Baseline to Final 2 Weeks (Average of Weeks 11 and 12) — 1.23; 0.60 Units on a Scale — p=0.0114
◆ Published Evidence
Established
29citations · ~3 / year
A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.
Pain · 2015 · Likely link

Summary

The primary objective of the study is to determine the analgesic efficacy and safety of ALO-02 extended-release capsules, when compared to placebo, in subjects with moderate to severe chronic low back pain.

Linked Publications (4)

  • A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.
    Pain · 2015 · 29 citations · Likely link
  • Patient-reported health-related quality of life, work productivity, and activity impairment during treatment with ALO-02 (extended-release oxycodone and sequestered naltrexone) for moderate-to-severe chronic low back pain.
    Health and quality of life outcomes · 2017 · 7 citations · Open access · Likely link
  • Effects of naltrexone exposure observed in two phase three studies with ALO-02, an extended-release oxycodone surrounding sequestered naltrexone.
    Journal of opioid management · 2019 · 3 citations · Likely link
  • Safety and tolerability of ALO-02 (oxycodone hydrochloride and sequestered naltrexone hydrochloride) extended-release capsules in older patients: a pooled analysis of two clinical trials.
    Current medical research and opinion · 2020 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Weekly Average Electronic Diary (eDiary) Numeric Rating Scale -Pain (NRS-Pain) Score From Randomization Baseline to Final 2 Weeks (Average of Weeks 11 and 12)
1.23; 0.60 0.0114 sig
SECONDARY
Change in Roland-Morris Disability Questionnaire (RMDQ) Total Score From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit).
0.50; 0.67 0.7547
SECONDARY
Percentage (%) of Participants With Shift in Patient Global Assessment (PGA) by Category With Baseline PGA Score of Very Good (1), Good (2), Fair (3), Poor (4), Very Poor (5) From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit).
5.4; 11.7; 6.2; 2.9; 1.5; 1.5 0.1272
SECONDARY
Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction of Greater or Equal to (≥) 20%
48.5; 62.3 0.0210 sig
SECONDARY
Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥30%
44.0; 57.5 0.0248 sig
SECONDARY
Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥40%
35.1; 50.7 0.0090 sig
SECONDARY
Percentage of Participants With Improvement in Weekly Average eDiary NRS-Pain Scores From Screening to Final 2 Weeks of the Double-Blind Treatment Period (Average of Weeks 11 and 12) by Cumulative Percent Reduction ≥50%
29.9; 39.7 0.0874
SECONDARY
Change From Screening Period to End of Open-Label Treatment in Brief Pain Inventory - Short Form (BPI-sf): Worst Pain, Least Pain, Average Pain, Pain Right Now, Pain Severity Index, Pain Interference Index
-3.3; -2.6; -3.0; -3.3; -3.1; -2.8 <0.0001 sig
SECONDARY
Change From Screening Period to Randomization Baseline in BPI-sf: Worst Pain, Least Pain, Average Pain, Pain Right Now, Pain Severity Index, Pain Interference Index
-4.2; -3.4; -3.8; -4.2; -3.9; -3.4 <0.0001 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Worst Pain
1.00; 0.38; 1.15; 0.51; 0.86; 0.49 0.0056 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Least Pain
0.74; 0.34; 0.94; 0.06; 0.83; 0.19 0.0412 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Average Pain
1.01; 0.36; 1.04; 0.30; 0.99; 0.35 0.0007 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Right Now
1.04; 0.40; 1.03; 0.24; 1.04; 0.33 0.0022 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Severity Index
0.95; 0.37; 1.04; 0.28; 0.95; 0.34 0.0022 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Interference Index
0.77; 0.36; 0.92; 0.43; 0.64; 0.47 0.0285 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Worst Pain
-3.09; -3.80; -3.01; -3.74; -3.16; -3.72 0.0061 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Least Pain
-2.55; -3.05; -2.40; -3.29; -2.44; -3.21 0.0250 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Average Pain
-2.63; -3.43; -2.76; -3.55; -2.71; -3.50 0.0002 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Right Now
-3.12; -3.72; -3.15; -3.82; -3.00; -3.71 0.0115 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Severity Index
-2.83; -3.50; -2.83; -3.60; -2.80; -3.53 0.0025 sig
SECONDARY
Change From Screening to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in BPI-sf Scores of Pain Interference Index
-2.58; -2.99; -2.52; -2.99; -2.72; -2.87 0.0727
SECONDARY
Area Under the Curve (AUC) of eDiary NRS-Pain Scores From Randomization Baseline to Final 2 Weeks of the Double-Blind Treatment Period (Weeks 11 and 12)
39.00; 11.25 0.0120 sig
SECONDARY
Average Daily Use of Rescue Acetaminophen (Milligrams Per Day [mg/Day]) During the Double-Blind Treatment Period
207.84; 203.97 0.9390
SECONDARY
Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment
85.2; 78.9; 67.3; 49.7
SECONDARY
Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to End of Open-Label Treatment
15; 21; 28; 35
SECONDARY
Percentage of Participants With a 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline
99.3; 95.3; 86.0; 64.0
SECONDARY
Median Time to 20%, 30%, 40%, or 50% Analgesic Response From Screening Period to Randomization Baseline
14; 20; 26; 33
SECONDARY
Percentage of Participants With a 20%, 30%, 40%, or 50% Loss of Analgesic Response From Randomization Baseline During the Double-Blind Treatment Period
72.0; 54.5; 64.4; 46.2; 57.6; 34.3
SECONDARY
Median Time to 20%, 30%, 40%, or 50% Loss of Analgesic Response From Baseline During the Double-Blind Treatment Period
12; 31; 21; NA; 41; NA 0.0014 sig
SECONDARY
Percentage of Participants Discontinuing Treatment for Investigator-Reported Lack of Efficacy
11.9; 2.7
SECONDARY
Median Time to Treatment Discontinuation for Investigator-Reported Lack of Efficacy During the Double-Blind Treatment Period
NA; NA 0.006 sig
SECONDARY
Clinical Opiate Withdrawal Scale (COWS) Total Score During the Open-Label Titration Period
0.6; 0.6; 0.0; 0.5; 0.0; 0.5
SECONDARY
COWS Total Score During the Double-Blind Treatment Period
0.6; 0.4; 0.8; 0.6; 0.3; 0.3
SECONDARY
COWS Total Score During the Post-Treatment Period
0.6; 0.6; 0.1; 0.2; 0.5; 0.9
SECONDARY
Percentage of Participants With Opiate Withdrawal During the Open-Label Titration Period by COWS Category
98.4; 1.6; 99.2; 0.8; 98.8; 1.2
SECONDARY
Percentage of Participants With Opiate Withdrawal During the Double-Blind Treatment Period by COWS Category
100; 100; 99.1; 98.5; 0; 1.5
SECONDARY
Percentage of Participants With Opiate Withdrawal During Post-Treatment by COWS Category
100.0; 100.0; 100; 95.6; 0; 4.4
SECONDARY
Subjective Opiate Withdrawal Scale (SOWS) During the Open-Label Titration Period
4.1; 3.5; -0.7; 3.0; -1.2; 2.7
SECONDARY
SOWS Total Score During the Double-Blind Treatment Period
2.4; 1.5; 3.0; 2.3; 0.6; 0.8
SECONDARY
SOWS Total Score During the Post-Treatment Period
2.6; 2.3; 0.2; 0.8; 2.7; 2.5
SECONDARY
Change From Screening Period to End of Open-Label Titration Period in Roland-Morris Disability Questionnaire (RMDQ) Total Score for All Participants
12.7; 9.0; -3.9 <0.0001 sig
SECONDARY
Change From Screening Period to Randomization Baseline in RMDQ Total Score
12.8; 7.9; -4.8 <0.0001 sig
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 2, 4, 8, and 12 (or Final Visit) in RMDQ Total Score
-3.88; -4.93; -3.90; -4.60; -4.50; -3.92 0.0733
SECONDARY
Change From Randomization Baseline to the End of Double-Blind Weeks 2, 4, and 8 in RMDQ Total Score
0.54; -0.19; 1.02; 0.32; -0.01; 0.41 0.1139
SECONDARY
Percentage of Participants With Shift From Screening to Randomization Baseline in PGA of Low Back Pain by Category in Participants With Screening PGA Score of Very Good, Good, Fair, Poor, Very Poor
0.4; 2.9; 9.4; 2.9; 0.0; 0.0 <0.0001 sig
SECONDARY
Percentage of Participants With Shift From Screening to the End of the Open-Label Titration Period in PGA of Low Back Pain by Category in Participants With Screening PGA Score of Very Good, Good, Fair, Poor, Very Poor
0.3; 2.7; 7.6; 2.2; 0.0; 0.0 <0.0001 sig
SECONDARY
Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Week 4 in PGA of Low Back Pain by Category in Participants With Randomization Baseline PGA Score of Very Good, Good, Fair, Poor, Very Poor
7.3; 8.7; 3.7; 0.8; 0.9; 0.0 0.2211
SECONDARY
Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Week 8 in PGA of Low Back Pain by Category in Participants With Randomization Baseline PGA Score of Very Good , Good, Fair, Poor, Very Poor
8.0; 8.9; 5.7; 3.6; 0.0; 1.8 0.5767
SECONDARY
Satisfaction With Treatment at the End of Open-Label Titration Period for All Participants
6.8; 7.0; 11.7; 40.7; 33.9
SECONDARY
Satisfaction With Treatment at Randomization Baseline
5.4; 2.2; 4.7; 46.0; 41.7
SECONDARY
Percentage of Participants Who Reported Being Satisfied/Very Satisfied With Treatment on the Satisfaction With Treatment Questionnaire During the Double-Blind Treatment Period
59.2; 79.7; 40.8; 20.3 0.0004 sig
SECONDARY
Change From Screening Period to the End of Open-Label Titration Period in Short Form-36v2 (SF-36v2) Health Survey Score
6.7; 7.7; 9.8; 2.3; 4.6; 5.0 <0.0001 sig
SECONDARY
Change From Screening Period to Randomization Baseline in SF-36v2 Health Survey Score
8.0; 9.1; 11.6; 3.1; 5.8; 7.0 <0.0001 sig
SECONDARY
Change From Randomization Baseline to the End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey
-2.06; -1.44; -2.56; -2.59; -5.07; -2.69 0.5181
SECONDARY
Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in SF-36v2 Health Survey
5.32; 6.84; 5.68; 6.78; 6.39; 8.78 0.1731
SECONDARY
Change From Screening Period to the End of Open-Label Titration Period in Participant Assessment of Overall Health State Using the EuroQol 5-Dimensions (EQ-5D) Summary Index
0.68; 0.80; 0.12 <0.0001 sig
SECONDARY
Change From Screening Period to the End of Open-Label Titration Period in Participant Assessment of Overall Health State Using the EQ-5D VAS
66.23; 74.69; 8.16 <0.0001 sig
SECONDARY
Change From Screening Period to Randomization Baseline in Participant Assessment of Overall Health State Using the EQ-5D Summary Index
0.68; 0.82; 0.14 <0.0001 sig
SECONDARY
Change From Screening Period to Randomization Baseline in Participant Assessment of Overall Health State Using the EQ-5D VAS
67.02; 76.85; 9.84 <0.0001 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D Summary Index
-0.061; -0.029 0.0605
SECONDARY
Change From Randomization Baseline to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using the EQ-5D VAS
-3.61; -2.89 0.7196
SECONDARY
Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D Summary Index
0.085; 0.106 0.2280
SECONDARY
Change From Screening Period to End of Double-Blind Week 12 (or Final Visit) in Participant Assessment of Overall Health State Using EQ-5D VAS
4.75; 7.01 0.2701
SECONDARY
Change From Screening Period to End of Open-Label in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP): % Work Time Missed, % Impairment, % Overall Work Impairment, % Activity Impairment Due to Low Back Pain
-1.3; -22.4; -21.6; -27.2 0.3822
SECONDARY
Change From Screening Period to Randomization Baseline in WPAI:SHP: Percent Work Time Missed, Percent Impairment, Percent Overall Work Impairment, Percent Activity Impairment Due to Low Back Pain
-4.9; -25.9; -26.9; -32.0 0.0017 sig
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Work Time Missed Due to Low Back Pain
3.54; -0.77; 4.29; 1.41; 6.49; 3.72 0.1389
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Impairment Due to Low Back Pain
5.22; -1.54; 3.63; -1.36; 6.77; 4.39 0.1201
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Overall Work Impairment Due to Low Back Pain
5.31; -2.03; 8.69; -0.66; 10.85; 5.71 0.1458
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Activity Impairment Due to Low Back Pain
6.23; 1.98; 2.05; 3.05; 10.56; 6.41 0.0768
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Work Time Missed Due to Low Back Pain
-0.09; -4.82; -1.42; -3.01; -1.00; -2.09 0.0926
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Impairment Due to Low Back Pain
-18.65; -31.03; -16.43; -29.37; -16.18; -25.38 0.0098 sig
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Overall Work Impairment Due to Low Back Pain
-19.84; -32.40; -15.21; -29.37; -15.16; -25.51 0.0177 sig
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in WPAI:SHP Percent Activity Impairment Due to Low Back Pain
-23.75; -31.24; -25.25; -29.87; -18.62; -26.81 0.0052 sig
SECONDARY
Percentage of Participants With Shift From Screening Period to End of Open-Label Titration Period in Hospitalization Because of Low Back Pain as Assessed Using the Healthcare Resource Use (HRU) Questionnaire
0.3; 0.8; 2.5; 96.4
SECONDARY
Percentage of Participants With Shift From Screening Period to Randomization Baseline in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire
0.4; 1.1; 2.9; 95.6
SECONDARY
Change From Screening to Randomization Baseline in HRU Questionnaire: Number of Office Visits Directly Related or Any Medication Used for Chronic Low Back Pain
11.4; 5.6; -4.7
SECONDARY
Change From Screening to Randomization Baseline in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks
84.7; 51.8; -41.8
SECONDARY
Change From Screening to Randomization Baseline in HRU Questionnaire: Nights Stayed in Hospital
0.1; 0.0; 0.0
SECONDARY
Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Number of Office Visits Directly Related or Any Medication Used for Chronic Low Back Pain
8.8; 5.4; -3.0
SECONDARY
Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Money Spent on Physical Treatments in Past 4 Weeks
104.1; 88.0; -28.3
SECONDARY
Change From Screening to End of Open-Label Titration Period in HRU Questionnaire: Nights Stayed in Hospital
0.1; 0.0; 0.0
SECONDARY
Percentage of Participants With Shift From Randomization Baseline to End of Double-Blind Weeks 4, 8, and 12 (or Final Visit) in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire
0.0; 0.0; 3.7; 0.8; 1.9; 0.0
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Number of Office Visits Related to or Medications Used for Chronic Low Back Pain
4.4; 6.6; 6.5; 5.3; 0.1; -3.1
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Money Spent on Treatments
96.4; 11.3; 19.9; 15.0; -24.7; 4.4
SECONDARY
Change From Randomization Baseline to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Nights Spent in Hospital
0.0; 0.0; 0.3; NA; NA; NA
SECONDARY
Percentage of Participants With Shift From Screening Period to the End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in Hospitalization Because of Low Back Pain as Assessed Using the HRU Questionnaire
0.9; 0.0; 2.8; 0.8; 2.8; 1.6
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Number of Office Visits Related or Medication Used for Chronic Low Back Pain
8.8; 13.7; 6.5; 5.3; 0.8; -7.6
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Money Spent on Treatment for Chronic Low Back Pain
83.6; 85.6; 19.9; 15.0; -79.8; -80.3
SECONDARY
Change From Screening Period to End of Double-Blind Weeks 4, 8 and 12 (or Final Visit) in HRU Questionnaire: Nights in Hospital for Chronic Low Back Pain
0.0; 0.3; 0.3; NA; 0.0; NA
SECONDARY
Mean Oxycodone Average Daily Dose During the Open-Label Titration Period
45.8
SECONDARY
Mean Oxycodone Duration of Titration During the Open-Label Titration Period
31.0
SECONDARY
Median Oxycodone Average Daily Dose During the Open-Label Titration Period
42.3
SECONDARY
Median Oxycodone Duration of Titration During the Open-Label Titration Period
35.0
SECONDARY
Mean Oxycodone Average Daily Dose During the Double-Blind Treatment Period
70.1; 63.6
SECONDARY
Mean Oxycodone Duration of Treatment During the Double-Blind Treatment Period
62.7; 70.9
SECONDARY
Median Oxycodone Average Daily Dose During the Double-Blind Treatment Period
60.0; 59.6
SECONDARY
Median Oxycodone Duration of Treatment During the Double-Blind Treatment Period
84.0; 85.0
SECONDARY
Oxycodone and Noroxycodone Observed Steady-State Plasma Concentration During the Titration Period
14.1; 26.4; 15.5; 29.9
SECONDARY
Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Titration Period
4.6; 14.6; 82.0; 154.1
SECONDARY
Oxycodone and Noroxycodone Observed Steady-State Plasma Concentration During the Double-Blind Treatment Period
27.0; 25.9; NA; 23.3; NA; 23.1
SECONDARY
Naltrexone and 6-β-naltrexol Observed Steady-State Plasma Concentration During the Double Blind Treatment Period
24.9; 5.3; 0.0; 3.4; 0.0; 2.9

Eligibility Criteria

Inclusion Criteria

  • Moderate-to-severe chronic low back pain present for at least 3 months.
  • Require a continuous around-the-clock opioid analgesic for an extended period of time.
  • Refrain from taking other opioid and non-opioid medications during the study.

Exclusion Criteria

  • Active or within a past 2 years a history of lumbosacral radiculopathy or chronic low back pain due to other underlying disorders such as spinal stenosis with neurologic impairment, cancer, infection, or post-surgical intervention.
  • Documented diagnosis of ongoing pain due to other chronic pain conditions which may interfere with assessment of chronic low back pain.
  • Active or ongoing or history of alcohol or drug abuse.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01571362) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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