BACKGROUND:Bupivacaine extended-release liposome injection is a novel formulation of bupivacaine designed to achieve long-acting postoperative analgesia.
OBJECTIVE:The aim of this study was to ...compare the magnitude and duration of postoperative analgesia from a single dose of bupivacaine extended-release injection with placebo administered intraoperatively in patients undergoing hemorrhoidectomy.
DESIGN:This evaluation was a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 study.
SETTINGS:Data were obtained from 13 centers in the Republic of Georgia, Poland, and Serbia.
PATIENTS:Included in this study were patients aged 18 to 86 years undergoing excisional hemorrhoidectomy.
INTERVENTIONS:All patients received either a single dose of bupivacaine extended-release 300 mg or placebo administered intraoperatively via wound infiltration.
MAIN OUTCOME MEASURE:The cumulative pain score was assessed by measurement of the area under the curve of pain intensity through 72 hours after study drug administration.
RESULTS:One hundred eighty-nine patients were randomly assigned and treated; 186 completed the study. Pain intensity scores were significantly lower in the bupivacaine extended-release group in comparison with the group receiving placebo (141.8 vs 202.5, P < .0001). More patients in the bupivacaine extended-release group remained opioid free from 12 hours (59%) to 72 hours (28%) after surgery compared with patients receiving placebo (14% and 10%; P < .0008 through 72 h). The mean total amount of opioids consumed through 72 hours was 22.3 mg and 29.1 mg in the bupivacaine extended-release and placebo groups (P ≤ .0006). The median time to first opioid use was 14.3 hours in the bupivacaine extended-release group vs 1.2 hours in the placebo group (P < .0001). A greater proportion of patients in the bupivacaine extended-release group were satisfied with their postsurgical analgesia (95% vs 73%, P = .0007) than in the placebo group.
CONCLUSIONS:Bupivacaine extended-release demonstrated a statistically significant reduction in pain through 72 hours, decreased opioid requirements, delayed time to first opioid use, and improved patient satisfaction compared with placebo after hemorrhoidectomy.
Cold agglutinin disease is a difficult-to-treat autoimmune hemolytic anemia in which immunoglobulin M antibodies bind to erythrocytes and fix complement, resulting in predominantly extravascular ...hemolysis. This trial tested the hypothesis that the anti-C1s antibody sutimlimab would ameliorate hemolytic anemia. Ten patients with cold agglutinin disease participated in the phase 1b component of a first-in-human trial. Patients received a test dose of 10-mg/kg sutimlimab followed by a full dose of 60 mg/kg 1 to 4 days later and 3 additional weekly doses of 60 mg/kg. All infusions were well tolerated without premedication. No drug-related serious adverse events were observed. Seven of 10 patients with cold agglutinin disease responded with a hemoglobin increase >2 g/dL. Sutimlimab rapidly increased hemoglobin levels by a median of 1.6 g/dL within the first week, and by a median of 3.9 g/dL (interquartile range, 1.3-4.5 g/dL; 95% confidence interval, 2.1-4.5) within 6 weeks (P = .005). Sutimlimab rapidly abrogated extravascular hemolysis, normalizing bilirubin levels within 24 hours in most patients and normalizing haptoglobin levels in 4 patients within 1 week. Hemolytic anemia recurred when drug levels were cleared from the circulation 3 to 4 weeks after the last dose of sutimlimab. Reexposure to sutimlimab in a named patient program recapitulated the control of hemolytic anemia. All 6 previously transfused patients became transfusion-free during treatment. Sutimlimab was safe, well tolerated, and rapidly stopped C1s complement–mediated hemolysis in patients with cold agglutinin disease, significantly increasing hemoglobin levels and precluding the need for transfusions. This trial was registered at www.clinicaltrials.gov as #NCT02502903.
•Seven of 10 patients with cold agglutinin disease responded to the anti-C1s antibody with a median 4-g/dL increase in hemoglobin levels.•Upstream inhibition of the classical complement cascade is an effective treatment for patients with cold agglutinin disease.
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Abstract
Objective:
Assess comparative efficacy of liposome bupivacaine administered at doses 266 mg and bupivacaine HCl administered at doses 200 mg for postsurgical analgesia.
Research design and ...methods:
Analysis of pooled efficacy and safety data from nine double-blind, placebo or active (bupivacaine HCl) controlled multimodal analgesia studies using a single dose of liposome bupivacaine or comparator, given via administration into the surgical site before end of surgery (i.e., inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Data from study arms that received liposome bupivacaine doses 266 mg were included.
Clinical trial registration:
Pooled data analysis includes nine studies: Study 1 - NCT01203644; Study 2 - NCT00485433; Study 3 - NCT00485693; Study 4 - NCT00529126; Study 5 - NCT00745290; Study 6 - NCT00744848; Study 7 - NCT00813111; Study 8 - NCT00890721; Study 9 - NCT00890682.
Main outcome measures:
Outcome measures included area under the curve (AUC) of pain intensity scores assessed by numeric rating scale (NRS) through 72 h postsurgery, time to first use of rescue opioid medications, total amount (mg) of opioid medications used, and occurrence of opioid-related adverse events (ORAEs). Incidence of overall AEs was also assessed.
Results:
Mean cumulative pain score (AUC of NRS through 72 h) was significantly lower with liposome bupivacaine (283) compared with bupivacaine HCl (329, p = 0.039). Median time from administration of study drug to first use of opioid rescue medication was significantly longer for liposome bupivacaine (10 h vs 3 h, p < 0.0001). Liposome bupivacaine was associated with a significant reduction in opioid use (12 mg vs 19 mg; p < 0.0001) and incidence of ORAEs (20% vs 36%; p < 0.0001), compared with bupivacaine HCl.
Conclusions:
In this pooled analysis from nine studies representing five different surgical procedures, liposome bupivacaine administered at doses 266 mg in a multimodal setting was associated with statistically significant and clinically meaningful lower cumulative pain score at 72 h, delayed and less consumption of opioids, and fewer ORAEs than bupivacaine HCl.
Abstract
Purpose
The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical ...control while receiving injectable somatostatin receptor ligands (SRLs).
Methods
In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 IGF-1 ≤ 1.0 × upper limit of normal ULN; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures.
Results
Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience.
Conclusions
OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.
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