Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

Introduction: This study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model.

Methods: This was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo.

APOLLO-2: A Randomized, Placebo and Active-Controlled Phase III Study Investigating Oliceridine (TRV130), a G Protein-Biased Ligand at the μ-Opioid Receptor, for Management of Moderate to Severe Acute Pain Following Abdominoplasty.

Objectives: The clinical utility of conventional IV opioids is limited by the occurrence of opioid-related adverse events. Oliceridine is a novel G protein-biased μ-opioid receptor agonist designed to provide analgesia with an improved safety and tolerability profile. This phase III, double-blind, randomized trial (APOLLO-2 [NCT02820324]) evaluated the efficacy and safety of oliceridine for acute pain following abdominoplasty.

Exploring the Interplay between Rescue Drugs, Data Imputation, and Study Outcomes: Conceptual Review and Qualitative Analysis of an Acute Pain Data Set.

In placebo-controlled acute surgical pain studies, provisions must be made for study subjects to receive adequate analgesic therapy. As such, most protocols allow study subjects to receive a pre-specified regimen of open-label analgesic drugs (rescue drugs) as needed. The selection of an appropriate rescue regimen is a critical experimental design choice.

Pregabalin for the treatment of postoperative pain: results from three controlled trials using different surgical models.

Purpose: To evaluate the efficacy and safety of pregabalin (150 or 300 mg/d) as an adjunctive therapy for the treatment of postoperative pain.

Patients And Methods: This study reports findings from three separate, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive pregabalin for the treatment of postoperative pain. Patients underwent one of three categories of surgical procedures (one procedure per study): elective inguinal hernia repair (post-IHR); elective total knee arthroplasty (post-TKA); or total abdominal hysterectomy (posthysterectomy).

A dose-finding study of sufentanil sublingual microtablets for the management of postoperative bunionectomy pain.

Background: Sufentanil sublingual microtablets (SSMs) at a dose of 15 µg per tablet have been studied for postoperative patient-controlled analgesia with a 20-minute lockout via a bedside handheld system over 2 days to 3 days of use. For more short-term (<24 hours) management of acute moderate-to-severe pain, such as in the ambulatory surgical setting, a single, higher-strength SSM dose administered via a health care provider would be of benefit as it would require less frequent administration and avoid the setup of a drug delivery system.

Methods: This study was a two-center, randomized, double-blind, placebo-controlled trial for 12 hours in patients 18 years to 80 years of age who were undergoing bunionectomy alone or with hammertoe repair.

IV acetaminophen: Efficacy of a single dose for postoperative pain after hip arthroplasty: subset data analysis of 2 unpublished randomized clinical trials.

Inadequate control of postoperative pain after orthopedic procedures may trigger complications that increase morbidity. Multimodal analgesia is used to manage pain effectively after surgical procedures and reduce the need for rescue analgesia. Intravenous (IV) acetaminophen (OFIRMEV; Cadence Pharmaceuticals, Inc.

A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery.

When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model.

Pharmacokinetics of sublingual sufentanil tablets and efficacy and safety in the management of postoperative pain.

Background And Objectives: A sublingual sufentanil tablet is being developed as a potential alternative to intravenous (IV) opioids for the management of postoperative pain. The objective of these studies was to evaluate the pharmacokinetics, efficacy, and safety of sublingual sufentanil tablets for postoperative pain management.

Methods: The pharmacokinetics of sublingual sufentanil 10 and 80 µg were compared with IV sufentanil in 12 subjects in a phase 1 study.

Safety and immunogenicity of recombinant human thrombin: a pooled analysis of results from 10 clinical trials.

Study Objective: To evaluate the safety and immunogenicity of recombinant human thrombin (rThrombin), an active topical stand-alone hemostatic agent.

Design: Analysis of pooled data from 10 rThrombin clinical trials.

Patients: A total of 644 adult and pediatric patients treated with rThrombin; 609 patients were included in the immunogenicity analysis.

Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen.

Background: This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen.

Methods: Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV(®) ; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol(®) 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall(®) 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg.

Immunogenicity and safety of re-exposure to recombinant human thrombin in surgical hemostasis.

Background: This Phase 4, open-label study evaluated the immunogenicity and safety of a second exposure to recombinant human thrombin (rThrombin) in adult patients with previous exposure to rThrombin.

Study Design: Topical rThrombin was applied as a hemostatic aid during a surgical procedure (day 1). Adverse events and clinical laboratory abnormalities were monitored to day 29 (study end).

A randomized, double-blind, placebo-controlled, multicenter, repeat-dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery.

Background: Intravenous acetaminophen has been approved in Europe and elsewhere for the treatment of acute pain and fever, and was recently approved by the US Food and Drug Administration (FDA) for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, and the reduction of fever.

Objective: The aim of this work was to evaluate the analgesic efficacy and safety of repeated doses of 2 dosing regimens of intravenous acetaminophen compared with placebo over 24 hours in subjects with moderate to severe pain after abdominal laparoscopic surgery.

Methods: This double-blind, placebo-controlled, parallel-group study was conducted at 17 sites in the United States and enrolled adult subjects (aged 18-80 years) who were randomized to 4 groups (IV acetaminophen 1000 mg [100 mL] q6h; IV acetaminophen 650 mg [65 mL] q4h; IV placebo 100 mL q6h; or IV placebo 65 mL q4h), each given as a 15-minute infusion after surgery for 24 hours.

Safety of multiple-dose intravenous acetaminophen in adult inpatients.

Background: Intravenous (IV) acetaminophen provides rapid and effective analgesia in the postoperative and inpatient settings. The utility and efficacy of acetaminophen is well established; however, due to chronic excessive dosing of over-the-counter acetaminophen products and prescription opioid combination products resulting in the potential for hepatic toxicity, concerns remain about acetaminophen safety. In order to evaluate the safety of IV acetaminophen 1,000mg q6h or 650mg q4h with repeated dosing for 5 days, a randomized, open-label study assessed the safety and tolerability of repeated doses used to treat acute pain or fever in 213 adult inpatients was conducted.

Persistence of antibodies to the topical hemostat bovine thrombin.

Background: Immunoassays that detect antibovine thrombin product antibodies are not widely available. However, knowing whether these antibodies are present preoperatively would be useful because re-exposure to bovine thrombin-containing products is contraindicated in patients with pre-existing antiproduct antibodies due to the risk of developing immune-mediated coagulopathies. In these exploratory analyses, we characterized one aspect of immune sensitization, the persistence of circulating antibodies after exposure to bovine thrombin product.

Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients.

Background: In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.

Methods: The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia.

Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin.

Background: We evaluated safety and immunogenicity observations pooled from 8 clinical trials of recombinant human thrombin (rThrombin), an active topical hemostatic agent.

Study Design: Recombinant thrombin was applied with an absorbable gelatin sponge or spray applicator during a surgical procedure (day 1). Adverse events and laboratory parameters were monitored until study end (day 29).

A phase 3b, open-label, single-group immunogenicity and safety study of topical recombinant thrombin in surgical hemostasis.

Background: The immunogenicity and safety of recombinant human thrombin (rThrombin) were evaluated in this phase 3b, open-label, single-group, multisite study of 209 adult vascular and spinal operation patients at high risk for preexisting anti-bovine thrombin product antibodies.

Study Design: Patients received rThrombin applied as a topical hemostat during a surgical procedure (day 1). Immunogenicity samples were collected at baseline and approximately 1 month after operation (day 29) and were analyzed after study participation.

Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery.

Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures.

Methods: The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up.