Complications with IV patient-controlled analgesia include programming errors, invasive access, and impairment of mobility. This study evaluated an investigational sufentanil sublingual tablet system ...(SSTS) for the management of pain after knee or hip arthroplasty.
This prospective, randomized, parallel-arm, double-blind study randomized postoperative patients at 34 U.S. sites to receive SSTS 15 μg (n = 315) or an identical placebo system (n = 104) and pain scores were recorded for up to 72 h. Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible. Patients were excluded if they were opioid tolerant. The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48 h. Secondary endpoints included total pain relief, patient and healthcare professional global assessments, and patient and nurse ease-of-care questionnaires.
Summed pain intensity difference (standard error) was higher (better) in the SSTS group compared with placebo (76 7 vs. -11 11, difference 88 95% CI, 66 to 109; P < 0.001). In the SSTS group, more patients and nurses responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001). Patient and nurse ease-of-care ratings for the system were high in both groups. There was a higher incidence of nausea and pruritus in the SSTS group.
SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals.
Abstract
Objective
To evaluate sufentanil sublingual tablet 30 mcg (SST 30 mcg) for postoperative pain in an older patient population with comorbidities.
Design
Multicenter, open-label, single-arm ...study.
Setting
Nine hospitals across the United States.
Subjects
Adults aged ≥40 years who had undergone a surgical procedure.
Methods
Patients with a postoperative pain intensity score ≥4 on an 11-point numeric rating scale (NRS) were allowed to enter the study and receive SST 30 mcg as requested for pain (minimum 60-minute redosing interval) over the 12-hour study period. Efficacy was assessed by patient reports of pain intensity on the NRS and a five-point pain relief scale. Safety was monitored throughout the study; plasma sufentanil concentrations were also measured. The primary efficacy endpoint was the time-weighted summed pain intensity difference (SPID) to baseline over 12 hours (SPID12).
Results
Of the 140 patients enrolled, 69% were American Society of Anesthesiologists Physical Class II or III, 44% had a body mass index (BMI) ≥30 mg/kg2, and 29% had hepatic and/or renal impairment. Average age was 54.7 years (SD = 9.9 years), and average baseline pain intensity was 6.2 (SD = 1.9). The most common surgeries were abdominal (59%) and orthopedic (20%). The mean SPID12 was 36.0 (standard error of the mean = 2.2); mean scores were similar, regardless of age, sex, race, and BMI. From baseline, mean pain intensity decreased significantly starting 30 minutes postdose, and mean pain relief increased significantly starting 15 minutes postdose, remaining relatively stable through 12 hours (P < 0.001 at each time point). Four (3%) patients discontinued due to inadequate analgesia, and 45 (32%) patients had one or more adverse events that were considered possibly or probably related to the study drug. Mean plasma sufentanil concentrations were generally similar regardless of age, sex, BMI, or organ impairment status.
Conclusions
SST 30 mcg was effective and well tolerated for the management of moderate-to-severe acute postoperative pain.
Abstract Purpose Sufentanil is a μ-opioid agonist with a high therapeutic index in preclinical studies and no active metabolites, and it is highly lipophilic, thereby enabling a transmucosal route of ...administration. Rapid distribution from the plasma after IV sufentanil administration results in a short duration of action requiring excessive repeated dosing if used for postoperative analgesia. The sufentanil sublingual tablet system (SSTS) is a handheld, preprogrammed, patient-controlled analgesia system designed to allow patients to self-administer sufentanil 15-μg tablets under their tongue with a 20-minute lockout. The pharmacokinetic (PK) characteristics of sufentanil, administered by different routes of delivery and after single and repeated sublingual (SL) administration, were examined in 2 studies. Methods A randomized, open-label, crossover study in healthy subjects evaluated the PK profile of sufentanil 15 μg administered by different routes: IV, SL, buccal (BU), and PO. A second open-label, crossover study in healthy subjects evaluated the PK parameters after single and repeated doses (full SSTS drug cartridge of 40 consecutive SL doses administered every 20 minutes) of a sufentanil 15-μg SL tablet. Doses were self-administered using the SSTS. Findings In the route of administration study (n = 25), mean Cmax values were highest with IV administration, and bioavailability values were: SL, 59%; BU, 78%; and PO, 9%. The absorption across the oral mucosa was associated with a median plasma half-time (time from Cmax to 50% of Cmax ) that was 25-fold longer (2.5 hours) with SL versus IV administration (0.1 hours). In the single- and repeated-dose study (n = 38), mean AUC0–∞ was 125.5 h · pg/mL, and Cmax was 35.0 pg/mL, with a median Tmax of 0.8 hours after the administration of a single sufentanil SL tablet. With 40 consecutive doses, Cmax was 8-fold higher compared with that of a single dose, and steady state was achieved after the 13th dose. Median plasma half-time after the 40th dose was not statistically longer than that after a single dose (2.7 vs 2.2 hours, respectively), and the median Tmax was 0.3 hours after the last repeated dose. Implications These study results support the viability of the SSTS for use in patient-controlled analgesia. The wide range of mean drug concentrations achieved after repeated dosing at 20-minute intervals compared with those with a single dose suggests the flexibility of patient-controlled dosing to meet individual analgesic requirements. The prolonged plasma half-time with SL administration is expected to provide a more appropriate duration of analgesia compared with that of IV administration, and the PK properties of repeated-dose administration support a 20-minute lockout interval.
BackgroundPharmacological properties of the sufentanil sublingual tablet 30mcg (SST 30mcg) could offer potential analgesic advantages in settings requiring noninvasive, acute pain management. The ...feasibility of using SST 30mcg for moderate-to-severe pain management in the emergency department (ED) was evaluated.MethodsThis open-label, multicenter feasibility study included patients aged ≥18years who presented to the ED with moderate-to-severe pain (≥4 on the numeric rating scale of pain intensity (NRS); opioid-tolerant patients were excluded. Patients received a single SST 30-mcg dose (single-dose cohort) or, upon request, ≤3 additional doses ≥60min apart (multiple-dose cohort) and were evaluated over 1 or 2h. Effectiveness was assessed by patient-reported pain scores (11-point NRS; 5-point pain relief scale). Safety and tolerability were also assessed.ResultsOverall, 76 patients enrolled into the single-dose (n=40) and multiple-dose (n=36) cohorts. In the first hour (combined cohorts), mean pain intensity was significantly lower 15-min post-dosing (P<0.001; clinically meaningful within 30-minutes post-dosing) and continued to decrease during the first hour (P<0.001 for each 15-minute interval). Mean pain intensity (multiple-dose cohort) decreased from 7.6 at baseline to 4.5 at 1h and to 4.6 at 2h (P<0.001 for both); mean pain relief increased from baseline to 1.9 at 1h (P<0.001) and to 2.0 at 2h (P<0.001). Most (79%) patients had no adverse events (AEs), and there were no severe AEs.ConclusionsSST 30mcg was feasible for managing moderate-to-severe acute pain in an ED setting.
Moderate-to-severe acute postoperative pain is commonly controlled with opioids administered via programmable intravenous (IV) patient-controlled analgesia (PCA) infusion pumps. Intravenously ...administered opioids provide effective relief of postoperative pain, and IV PCA enables patients to control their level of analgesia, which has advantages over nurse-administered approaches, including more satisfied patients and improved pain relief. Unfortunately, commonly used opioid analgesics can cause significant adverse effects. Furthermore, IV PCA has drawbacks, such as device programming errors, system errors, medication errors, limitations in patient mobility, and potential for IV tubing kinks, clogging, and transmission of infection. The IV route of administration is also characterized by a rapid, high peak in analgesic drug concentration followed by rapidly decreasing concentrations. Consequently, respiratory depression, excessive sedation, and inadequate pain control can occur. Furthermore, the technical assembly of an infusion pump is often complex and time-consuming. PCA modalities that incorporate superior opioid analgesics, such as sufentanil, and novel noninvasive routes of administration offer great promise for enhancing the patient and caregiver experience with the use of postoperative PCA.
Background
Results from a phase‐3, prospective, randomized, double‐blind, placebo‐controlled trial evaluating sufentanil sublingual tablet 30 mcg (SST) for the management of pain after ambulatory ...abdominal surgery are presented.
Methods
Adults with American Society of Anesthesiologists status 1 to 3 scheduled to undergo abdominoplasty, open tension‐free inguinal hernioplasty, or laparoscopic abdominal surgery under general or spinal anesthesia that did not include intrathecal opioids during the operation were eligible. Opioid‐tolerant patients were excluded. The primary endpoint was the time‐weighted summed pain intensity difference to baseline (SPID) over 12 hours. Secondary endpoints included SPID over 24 and 48 hours, total pain relief, and patient and healthcare professional (HCP) global assessments.
Results
Overall, 161 patients were randomized to SST (N = 107) or placebo (N = 54); pain scores were recorded for up to 48 hours. SPID 12 was higher (greater pain intensity reduction from baseline) in the SST group compared with placebo (25.8 vs. 13.1; P < 0.001, with a difference of 12.7 95% confidence interval 7.16, 18.23). In the SST group, a greater proportion of patients and HCPs responded “good” or “excellent” on the global assessments compared with placebo (P < 0.001 for both). There was a numerically, but not statistically, higher incidence of nausea and headache in the SST group.
Conclusions
In patients following abdominal surgery in an ambulatory care setting, SST was an effective opioid analgesic in postoperative pain management. In addition, SST was well tolerated with mild‐to‐moderate side effects, similar to those found in placebo‐treated patients.
Background
Problems with intravenous patient‐controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to ...evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20‐minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6‐minute lockout interval (IV PCA MS) for the management of acute postoperative pain.
Methods
This was a randomized, open‐label, 48‐hour non‐inferiority study with optional extension to 72 hours at 26 U.S. sites enrolling patients scheduled for elective major open abdominal or orthopedic (hip or knee replacement) surgery. The primary outcome measure was the proportion of patients who responded “good” or “excellent” (collectively “success”) at the 48‐hour timepoint on the Patient Global Assessment of method of pain control (PGA48).
Results
A total of 357 patients received study drug and 78.5% vs. 65.6% of patients achieved PGA48 “success” for SSTS vs. IV PCA MS, respectively, demonstrating non‐inferiority (P < 0.001 using the one‐side Z‐test against the non‐inferiority margin) as well as statistical superiority for treatment effect (P = 0.007). Patients using SSTS reported more rapid onset of analgesia and patient and nurse ease of care and satisfaction scores were higher than IV PCA MS. Adverse events were similar between the 2 groups; however, SSTS had fewer patients experiencing oxygen desaturations below 95% compared to IV PCA MS (P = 0.028).
Conclusions
Sufentanil sublingual tablet system is a promising new analgesic technology that may address some of the concerns with IV PCA.
This study evaluates the efficacy and safety of a sufentanil sublingual tablet system (SSTS) for the management of postoperative pain following open abdominal surgery.
At 13 hospital sites in the ...United States, patients following surgery with pain intensity of greater than 4 on an 11-point numerical rating scale were randomized to receive SSTS dispensing a 15-μg sufentanil tablet sublingually with a 20-minute lockout or an identical system dispensing a placebo tablet sublingually. Pain intensity scores were recorded at baseline and for up to 72 hours after starting study drug. The primary end point was time-weighted summed pain intensity difference (SPID) over 48 hours. Secondary end points included SPID and total pain relief (TOTPAR) for up to 72 hours and patient and health care provider global assessments of the method of pain control.
Summed pain intensity difference over 48 hours was significantly higher in the SSTS group than in the placebo group (least squares mean SEM, 105.60 10.14 vs 55.58 13.11; P = 0.001). Mean SPID and TOTPAR scores were significantly higher in the SSTS group at all time points from 1 hour (SPID) or 2 hours (TOTPAR) until 72 hours (P < 0.05). In the SSTS group, patient global assessment and health care provider global assessment ratings of good or excellent were greater than placebo at all time points (P < 0.01). Safety parameters, including adverse events and vital signs, were similar for SSTS and placebo.
These results suggest that SSTS is effective and safe for the management of postoperative pain in patients following open abdominal surgery.
To aid nurses in dosing sufentanil sublingual tablet (SST) 30 mcg administered via a single-dose applicator, dosing requirements and efficacy of SST 30 mcg were analyzed across age, sex, race, and ...body mass index subgroups.
Patient characteristics were pooled from three postoperative studies (two placebo-controlled and one open-label) and one open-label emergency department study. Drug dosing and efficacy data were pooled from the postoperative studies.
Efficacy was assessed through summed pain intensity difference to baseline during 12 hours across subgroups.
Mean (standard deviation) drug doses administered from 0 to 12 hours was 3.9 (2.0) for SST 30 mcg and was less frequent for older (≥65 years) versus younger patients. The summed pain intensity difference to baseline during 12 hours was superior with SST 30 mcg versus placebo across all subgroups.
SST 30 mcg is a sublingual opioid analgesic with efficacy across demographic subgroups.
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