Trial Outcomes & Findings for Efficacy and Safety Trial to Evaluate the Sufentanil NanoTab® PCA System/15 mcg (Zalviso™) for Post-Operative Pain in Patients After Knee or Hip Replacement Surgery (NCT NCT01660763)
NCT ID: NCT01660763
Last Updated: 2015-10-20
Results Overview
SPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417. Time-weighted SPID48 = ∑ \[T(i) - T(i-1)\] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
419 participants
Primary outcome timeframe
48 hours
Results posted on
2015-10-20
Participant Flow
Recruitment period of 9 months - August 2012 through April 2013
Patients were excluded per protocol exclusion criteria at Screening as well as post surgery for certain conditions including the following: 1. Patients who were not awake or stable 2. Patients with arterial oxygen saturation that couldn't be maintained at 95% or greater 3. Patients with uncontrollable vomiting
Participant milestones
| Measure |
Sufentanil NanoTab PCA System/15 mcg
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours
|
Placebo Sufentanil NanoTab PCA System
Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours
|
|---|---|---|
|
Overall Study
STARTED
|
315
|
104
|
|
Overall Study
COMPLETED
|
215
|
43
|
|
Overall Study
NOT COMPLETED
|
100
|
61
|
Reasons for withdrawal
| Measure |
Sufentanil NanoTab PCA System/15 mcg
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours
|
Placebo Sufentanil NanoTab PCA System
Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours and up to 72 hours
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
45
|
50
|
|
Overall Study
Adverse Event
|
22
|
7
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
|
Overall Study
Patient ready for early discharge
|
28
|
4
|
Baseline Characteristics
Efficacy and Safety Trial to Evaluate the Sufentanil NanoTab® PCA System/15 mcg (Zalviso™) for Post-Operative Pain in Patients After Knee or Hip Replacement Surgery
Baseline characteristics by cohort
| Measure |
Sufentanil NanoTab PCA System/15 mcg
n=315 Participants
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours
|
Placebo Sufentanil NanoTab PCA System
n=104 Participants
Placebo Sufentanil NanoTab PCA System : Placebo NanoTab dosed sublingually q 20 minutes as needed for pain for at least 48 hours. Patient may elect to remain in study for up to 72 hours
|
Total
n=419 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
|
129 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
179 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
186 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
240 Participants
n=5 Participants
|
|
Age, Continuous
|
66.6 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
65.0 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
66.2 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
188 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
254 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
127 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
315 participants
n=5 Participants
|
104 participants
n=7 Participants
|
419 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 hoursSPID-48 is the sum of the pain intensity difference (PID) over the 48 hour time period. A pain intensity score of 0 (no pain) to 10 (worse possible pain) is obtained before starting the study and throughout the 48 time period. The pain score at each assessment time is subtracted from the baseline pain score to provide the total sum score or SPID-48. A higher SPID-48 is better and indicates a reduction in pain intensity compared to the baseline score. Range of SPID48 scores were -239 to 417. Time-weighted SPID48 = ∑ \[T(i) - T(i-1)\] x PID(i), where T(0) = Time 0 (baseline), T(i) is the scheduled or unscheduled assessment time, and PID(i) is the PID score at time i for i=0 to 48 hours
Outcome measures
| Measure |
Sufentanil NanoTab PCA System/15 mcg
n=315 Participants
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
Placebo Sufentanil NanoTab PCA System
n=104 Participants
Placebo Sufentanil NanoTab PCA System/15 mcg : Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
|---|---|---|
|
Time-weighted Summed Pain Intensity Difference (SPID) Over the 48-hour Study Period (SPID48).
|
76.24 Units on a scale
Standard Error 7.02
|
-11.35 Units on a scale
Standard Error 10.55
|
Adverse Events
Sufentanil NanoTab PCA System/15 mcg
Serious events: 8 serious events
Other events: 171 other events
Deaths: 0 deaths
Placebo Sufentanil NanoTab PCA System
Serious events: 4 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sufentanil NanoTab PCA System/15 mcg
n=315 participants at risk
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
Placebo Sufentanil NanoTab PCA System
n=104 participants at risk
Placebo Sufentanil NanoTab PCA System/15 mcg : Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
|---|---|---|
|
Renal and urinary disorders
Acute Renal Failure
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Respiratory, thoracic and mediastinal disorders
Apnoea
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Cardiac disorders
Atrial Fibrillation
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
1.9%
2/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Infections and infestations
Cellulitis
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Investigations
Coagulopathy
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Psychiatric disorders
Confusional State
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Musculoskeletal and connective tissue disorders
Epididymitis
|
0.00%
0/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Gastrointestinal disorders
Fecal Infection
|
0.00%
0/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Investigations
Hypoxia
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Investigations
Oxygen Saturation Decreased
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Cardiac disorders
Sinus Tachycardia
|
0.32%
1/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Renal and urinary disorders
Urinary Tract Infection
|
0.00%
0/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
Other adverse events
| Measure |
Sufentanil NanoTab PCA System/15 mcg
n=315 participants at risk
Sufentanil NanoTab PCA System/15 mcg : 15 mcg Sufentanil NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
Placebo Sufentanil NanoTab PCA System
n=104 participants at risk
Placebo Sufentanil NanoTab PCA System/15 mcg : Placebo NanoTab dosed sublingually every 20 minutes as needed for pain for up to 48 hours. Patients may elect to remain in study for up to 72 hours.
|
|---|---|---|
|
Psychiatric disorders
Confusional State
|
2.5%
8/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Gastrointestinal disorders
Constipation
|
4.8%
15/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Nervous system disorders
Dizziness
|
5.1%
16/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.96%
1/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Gastrointestinal disorders
Dry Mouth
|
1.3%
4/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Nervous system disorders
Headache
|
4.1%
13/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
5.8%
6/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Vascular disorders
Hypotension
|
3.8%
12/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
1.9%
2/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Psychiatric disorders
Insomnia
|
4.1%
13/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
2.9%
3/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Gastrointestinal disorders
Nausea
|
34.9%
110/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
22.1%
23/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Vascular disorders
Orthostatic Hypotension
|
1.3%
4/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
1.9%
2/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Investigations
Oxygen Saturation Decreased
|
7.0%
22/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
2.9%
3/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.8%
15/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
General disorders
Pyrexia
|
1.3%
4/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
1.9%
2/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Nervous system disorders
Sedation
|
1.3%
4/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
0.00%
0/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
34/315 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
5.8%
6/104 • AEs were collected from time of first study drug dose taken through 12 hours after last study drug dose taken.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60