Ramosetron Group Research Articles

Ramosetron as an add-on therapy for refractory fibromyalgia: a randomized, double-blind, placebo-controlled trial.

This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10 and 28. Safety was continuously monitored throughout the study. At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, P < 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, P < 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, P < 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

Effect of dexamethasone and ramosetron on the prevention of postoperative nausea and vomiting in low-risk patients: a randomized, double-blind, placebo-controlled, multicenter trial

BackgroundSeveral studies have investigated the effect of antiemetics on postoperative nausea and vomiting (PONV) in high-risk groups. However, few studies have investigated the effect of antiemetics in patients at low risk of developing PONV.MethodsIn this prospective, randomized, double-blinded trial, 177 patients undergoing surgery under general anesthesia were randomly allocated to three groups. Patients allocated to group C (control group) received 2 mL of intravenous 0.9% saline, those allocated to group R (ramosetron group) received 0.3 mg of intravenous ramosetron, and those allocated to group DR (ramosetron plus dexamethasone group) received 5 mg of intravenous dexamethasone and 0.3 mg of intravenous ramosetron.ResultsFinally, 174 patients completed the study, and the types of surgeries were orthopedic (n = 80), rhinologic (n = 47), urologic (n = 29), and others (n = 18). The incidence of PONV up to 48 h postoperatively was significantly lower in group DR than in group C. The incidence of PONV up to 0–1 h postoperatively was significantly lower in groups R and DR than in group C. The usage pattern of rescue antiemetics was consistent with the incidence of PONV. The percentage of patients requiring rescue analgesics 0–1 h postoperatively was significantly lower in groups R and DR than in group C.ConclusionsThe combination of dexamethasone and ramosetron demonstrated a superior effect in preventing PONV for 48 h after surgery under general anesthesia than saline in patients at low risk of developing PONV. Compared with saline injections, ramosetron injections yielded better outcomes for the incidence of PONV and the use of rescue antiemetics and rescue analgesics 0–1 h postoperatively.Trial registrationClinical trial registration number: criskorea@korea.kr, KCT0006749.

Comparison of the Effectiveness of Palonosetron and Ramosetron in Preventing Postoperative Nausea and Vomiting: Updated Systematic Review and Meta-Analysis with Trial Sequential Analysis.

This updated systematic review and meta-analysis with trial sequential analysis aimed to compare the efficacy of the perioperative administration of palonosetron with that of ramosetron in preventing postoperative nausea and vomiting (PONV). A total of 17 randomized controlled trials comparing the efficacy of the perioperative administration of palonosetron to that of ramosetron for preventing PONV were included. The primary outcomes were the incidences of postoperative nausea (PON), postoperative vomiting (POV), and PONV, which were measured in early, late, and overall phases. Subgroup analysis was performed on the basis of the administration time of the 5-HT3 receptor antagonist and divided into two phases: early phase and the end of surgery. A total of 17 studies with 1823 patients were included in the final analysis. The incidence of retching (relative risk [RR] = 0.525; 95% confidence interval [CI] = 0.390 to 0.707) and late POV (RR = 0.604; 95% CI = 0.404 to 0.903) was significantly lower in the palonosetron group than in the ramosetron group. No significant differences were demonstrated in the incidence of PON, PONV, complete response, use of antiemetics, and adverse effects. Subgroup analysis showed that palonosetron was superior to ramosetron in terms of early PON, late PON, overall POV, and use of rescue antiemetics when they were administered early; in terms of retching, regardless of the timing of administration. Ramosetron was superior to palonosetron in terms of early PON when they were administered late. The prophylactic administration of palonosetron was more effective than that of ramosetron in preventing the development of retching and late POV. In this meta-analysis, no significant differences in PONV prevention between the two drugs were demonstrated. Further studies are required to validate the outcomes of our study.

Efficacy of Serotonin Type 3 Receptor Antagonist Ramosetron on Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)-Like Symptoms in Patients with Quiescent Inflammatory Bowel Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

Patients with quiescent inflammatory bowel disease (IBD) frequently suffer diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms, such as abdominal pain or stool irregularities. Here, we assessed the effect of ramosetron, a serotonin type 3 (5-HT3) receptor antagonist, on IBS-D-like symptoms in patients with quiescent IBD. Seventy patients with quiescent IBD, who met the Rome III diagnostic criteria for IBS-D, were randomly assigned to receive either ramosetron (5 μg; n = 35) or a placebo (n = 35) orally once daily for 4 weeks. The primary endpoint was the responder rate for global assessment of relief from overall IBS-D-like symptoms. The responder rates for relief of abdominal pain/discomfort and improvement of bowel habits were also evaluated. The responder rate for relief from overall IBS-D-like symptoms at the final evaluation point was significantly higher in the ramosetron group (35.5%) than in the placebo group (11.4%) (p = 0.037). The responder rate for improvement of bowel habits was significantly higher in the ramosetron group (38.7%) than in the placebo group (14.3%) (p = 0.028). The reduction of stool frequency was significantly greater in the ramosetron group than in the placebo group (p = 0.044). Ramosetron is effective for relief of overall IBS-D-like symptoms in patients with quiescent IBD.

Heart-Rate-Corrected QT Interval Response to Ramosetron during Robot-Assisted Laparoscopic Prostatectomy: A Randomized Trial.

Ramosetron, often used to prevent postoperative nausea and vomiting, might cause heart-rate-corrected (QTc) interval prolongation, as might robot-assisted laparoscopic prostatectomy (RALP), which requires a steep Trendelenburg position and CO2 pneumoperitoneum. This study aimed to determine how ramosetron administration affects the QTc interval in patients treated with RALP. Fifty-six subjects were randomly assigned to ramosetron (n = 28) or control (n = 28) groups. The ramosetron group received 0.3 mg of ramosetron after anesthetic induction, whereas the control group received normal saline. The QTc interval was measured before and after induction; after 5, 30, and 60 min of being placed in the Trendelenburg position; immediately after being returned to a supine position; and at the end of surgery. Linear mixed models were used to compare QT intervals between groups. QTc intervals did not differ significantly between groups over time (Pgroup×time = 0.111). However, they increased significantly in both groups after placement in the Trendelenburg position compared with before induction (Ptime < 0.001). This increase in QTc continued until the end of surgery in both groups. Based on these findings, ramosetron can be safely administered for the prevention of postoperative nausea and vomiting among patients undergoing RALP.

Effects of ramosetron orally disintegrating tablets on the prophylaxis of post-discharge nausea and/or vomiting in female patients undergoing day surgery under general anesthesia: a randomized controlled trial

BackgroundThis study was performed to evaluate the effectiveness of ramosetron orally disintegrating tablets (ODTs) in preventing post-discharge nausea and/or vomiting (PDNV) in female patients following outpatient surgery under general anesthesia.MethodsThis multicenter randomized study included three South Korean tertiary hospitals. Before surgery, 138 patients were randomly allocated into two groups. In the ramosetron group, ramosetron ODT 0.1 mg was administered after discharge in the morning of postoperative days 1 and 2. Metoclopramide 10 mg was administered as a rescue antiemetic (capped at 30 mg per day). In the control group, patients were administered only metoclopramide 10 mg when nausea and/or vomiting occurred. The primary outcome was the incidence of nausea during 24 h after discharge.ResultsWe found significant differences in the incidence (13% vs. 33%, P = 0.008) and severity (P = 0.011) of nausea between the ramosetron and the control groups during 24 h after discharge. In addition, the rate of rescue antiemetic (metoclopramide) administration during 24 h after discharge was lower in the ramosetron group (6%) than in the control group (18%) (P = 0.033). Patient satisfaction score was higher in the ramosetron group than in the control group (P < 0.001).ConclusionRamosetron ODT reduces the incidence and severity of postoperative nausea after discharge during the first 24 h and may be a valuable option for the prevention of PDNV in female patients after day surgery under general anesthesia.Trial registrationClinicalTrials.gov, NCT04297293. Registered on 05 March 2020

The Effect of Ramosetron on Remifentanil in Preventing Emergence Cough from Sevoflurane Anesthesia in Female Patients.

Remifentanil reduces cough during extubation. Ramosetron, a 5-HT3 receptor antagonist, is a potent antiemetic. Regarding the antitussive property of 5-HT receptor agonists, ramosetron can mediate the cough reflex by increasing the remifentanil requirement. This study evaluated the effect of ramosetron on the optimal effect-site concentration (Ce) of remifentanil for preventing emergence cough from sevoflurane anesthesia in female patients. Forty-seven randomly selected female patients undergoing laparoscopic cholecystectomy received either ramosetron 0.3 mg (n = 23) or the same volume of normal saline (n = 24) intravenously at the end of surgery. The remifentanil Ce using target-controlled infusion in 50% of patients (EC50) and 95% of patients (EC95) were assessed using Dixon's up-and-down or isotonic regression method with a bootstrapping approach. Using Dixon's up-and-down method, the EC50 of remifentanil in the control group (1.33 ± 0.38 ng/mL) was comparable to that of ramosetron group (1.50 ± 0.69 ng/mL) (P = 0.615). Using isotonic regression analysis, the EC50 (83% confidence interval) did not differ between the two groups (1.17 [0.86-1.43] ng/mL and 1.13 [0.68-1.56] ng/mL in control and ramosetron groups). However, the EC95 (95% confidence interval) was significantly lower in the control group than in the ramosetron group (1.90 [1.45-1.96] ng/mL and 2.92 [2.35-2.97] ng/mL). Remifentanil Ce for preventing emergence cough was higher in the ramosetron group than in the control group. It may indicate the lowering effect of ramosetron on the antitussive activity of remifentanil.

Antiemetic Prophylaxis with Ramosetron for Postoperative Nausea and Vomiting in Patients Undergoing Microvascular Decompression : A Prospective, Randomized Controlled Trial

This prospective, randomized, double-blinded trial aimed to evaluate the efficacy and safety of prophylactic ramosetron administration against postoperative nausea and vomiting (PONV) in patients undergoing microvascular decompression (MVD). In this study, 100 patients undergoing MVD were randomly allocated to the control (normal saline, 2 mL) or ramosetron (ramosetron, 0.3 mg) groups at the end of surgery. The incidence and severity of PONV, need for rescue antiemetics, patient satisfaction score, duration of hospital stay, and the occurrence of adverse events were evaluated 48 hours post-surgery. Data obtained from 97 patients were included in the final analysis. The incidence of PONV was significantly lower in the ramosetron group than in the control group throughout the 48-hour postoperative period (29.2% vs. 51.0%, p=0.028). A similar trend was observed with regard to PONV severity (p=0.041). The need for rescue antiemetics, satisfaction score, duration of hospital stays, and the occurrence of adverse events did not significantly differ between the groups. Prophylactic ramosetron administration reduced the incidence and severity of PONV in patients undergoing MVD without causing serious adverse events. Thus, ramosetron use may improve patient recovery following MVD.

A comparative clinical study of methylprednisolone with ondansetron versus methylprednisolone with ramosetron in preventing postoperative nausea and vomiting in patients undergoing middle ear surgeries

Background: Postoperative nausea and vomiting (PONV) is one of the most unpleasant complications of anaesthesia and is more common following middle ear surgeries. Ondansetron, a 5-HT3 (5-hydroxytryptamine type 3) receptor antagonist provides significant reduction in early PONV. The other 5-HT3 antagonist ramosetron, with long duration of action, has been found to be more effective than ondansetron in reducing the early as well as delayed PONV. The antiemetic effects of glucocorticoids (dexamethasone and methylprednisolone) are well documented. So, the present study was designed to compare the efficacy of the combination of intravenous methylprednisolone and ondansetron with combination of intravenous methylprednisolone and ramosterone in preventing postoperative nausea and vomiting in patients undergoing middle ear surgeries. Methods: Sixty patients in the age group of 18-60 years, with American Society of Anaesthesiologists (ASA) physical status classification I or II, undergoing middle ear surgery were randomly allocated to receive a combination of methylprednisolone 40 mg (given at the beginning of surgery) and ondansetron 4 mg (given near the end of surgery) (group MO, n=30) or combination of intravenous methylprednisolone 40 mg and ramosetron 0.3 mg (near the end of surgery) (group R, n=30), by a computer-generated randomization table. Incidence of PONV in the both groups were studied and compared. Results: There was no significant difference in PONV between the groups in the first 2 h after the surgery. Between 2 and 24 h, the incidence of nausea was significantly lower in the methylprednisolone and ondansetron group compared to the methylprednisolone and ramosetron group (P=0.01). Between 24 and 48 h, there was no difference between the two groups with respect to incidence of nausea and vomiting. Conclusion: The combination of methylprednisolone and ondansetron is superior to combination of methylprednisolone and ramosetron for prevention of PONV after middle ear surgery especially in treatment of early PONV. Therefore, we recommend combination of methylprednisolone and ondansetron for prophylaxis for PONV in middle ear surgeries.

Anterior resection syndrome: a randomized clinical trial of a 5-HT3 receptor antagonist (ramosetron) in male patients with rectal cancer.

No effective treatment exists for anterior resection syndrome (ARS) following sphincter-saving surgery for rectal cancer. This RCT assessed the safety and efficacy of a 5-HT3 receptor antagonist, ramosetron, for ARS. A single-centre, randomized, controlled, open-label, parallel group trial was conducted. Male patients with ARS 1 month after rectal cancer surgery or ileostomy reversal were enrolled and randomly assigned (1 : 1) to 5 μg of ramosetron (Irribow®) daily or conservative treatment for 4 weeks. Low ARS (LARS) score was calculated after randomization and 4 weeks after treatment. The study was designed as a superiority test with a primary endpoint of the proportion of patients with major LARS between the groups. Primary outcome analysis was based on the modified intention-to-treat population. Safety was assessed by monitoring adverse events during the study. : A total of 100 patients were randomized to the ramosetron (49 patients) or conservative treatment group (51 patients). Two patients were excluded, and 48 and 50 patients were analysed in the ramosetron and control groups, respectively. The proportion of major LARS after 4 weeks was 58 per cent (28 of 48 patients) in the ramosetron group versus 82 per cent (41 of 50 patients) in the control group, with a difference of 23.7 per cent (95 per cent c.i. 5.58 to 39.98, P = 0.011). There were minor adverse events in five patients, which were hard stool, frequent stool or anal pain. These were not different between the two groups. There were no serious adverse events. : Ramosetron could be safe and feasible for male patients with ARS. NCT02869984 (http://www.clinicaltrials.gov).

Comparison of intravenous ramosetron and ondansetron as prophylaxis for postoperative nausea and vomiting following general anesthesia

Objective: To compare the efficacy and side effects of 5HT3 antagonists, ramosetron, and ondansetron as prophylaxis for postoperative nausea and vomiting (PONV) following general anesthesia. Materials and Methods: One hundred and ten patients of the American Society of Anesthesiology Grade I–II, between the age group of 18 to 60 years weighing 40 to 70 kg, undergoing general anesthesia were studied. Group 1 received ramosetron 0.3 mg intravenous (IV) and Group 2 received ondansetron 8 mg IV 15 min before the end of surgery. The incidence of PONV, need for rescue antiemetic, and side effects were evaluated in both the groups. QTc interval prolongation was also evaluated in both the groups by taking electrocardiograms at regular intervals. Results: This study showed that there was no statistically significant difference in the incidence of PONV between the ondansetron group and the ramosetron group during the first 24 h after surgery. For PONV score of ≥2 during the first 6 h, the incidence was 3.59% and 1.81% for ramosetron and ondansetron, respectively, and during 6–24 h, the incidence was 1.81% for both the drugs. Conclusion: IV ramosetron 0.3 mg is as effective as IV ondansetron 8 mg in preventing PONV in patients undergoing general anesthesia.

The effectiveness of ramosetron and ondansetron for preventing postoperative nausea and vomiting after arthroscopic rotator cuff repair: a randomized controlled trial

BackgroundArthroscopic rotator cuff repair is a painful procedure, and treatment of emetic events associated with drugs used in the current multimodal pain management remains challenging. This study aimed to evaluate the effectiveness of ramosetron or ondansetron to relieve postoperative nausea and vomiting (PONV) and pain after arthroscopic rotator cuff repair.MethodsIn total, 122 consecutive patients undergoing arthroscopic rotator cuff repair were randomly allocated into three groups: ramosetron group (n = 39), ondansetron group (n = 43), and control group (n = 40). Then, 0.3 mg of ramosetron or 8 mg of ondansetron was administered intravenously at the end of surgery according to group. All patients received general anesthesia and multimodal pain management protocol including preemptive analgesic medication, fentanyl-based intravenous patient-controlled analgesia, and postoperative analgesic medication. Incidence of emetic events, rescue antiemetic requirements (10 mg of metoclopramide, IV), complete response, pain level, and side effects were recorded in three periods: 0–6, 6–24, and 24–48 h postoperatively. The severity of nausea and pain was evaluated using a visual analog scale.ResultsThe ramosetron group tended to have a lower incidence and severity of nausea during the 6- to 24-h postoperative period and fewer rescue antiemetic drug requirements during the 0- to 48-h period than the control group, showing statistical significance. Additionally, the frequency of complete response of the ramosetron and ondansetron groups was significantly higher than that of the control group. No difference was found among the groups in the pain level except during the 0- to 6-h period. The two groups have a higher complete response during the 6- to 24-h period than the control group.ConclusionsRamosetron use led to a lower incidence, mild severity of nausea, and reduced use of rescue antiemetic drug after arthroscopic rotator cuff repair during the 6- to 24-h postoperative period than the control.Level of evidenceLevel I, randomized controlled trials, treatment study

Low-dose ramosetron accelerates gastric emptying in the early phase: A crossover study in healthy volunteers using a continuous real-time 13C breath test (BreathID System).

The aim of this study was to determine the correlation between low-dose ramosetron pre-treatment and gastric emptying using a novel, non-invasive technique for measuring gastric emptying, namely, the continuous real-time 13C breath test (BreathID system: Exalenz Bioscience Ltd., Israel). Twelve healthy male volunteers participated in this randomized two-way crossover study. The subjects fasted overnight and were randomly assigned to receive the test meal (200 kcal per 200 mL) after an hour pre-treatment with 5 µg ramosetron or the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal with the 13C-acetic acid breath test performed continuously using the BreathID system. Using Oridion Research Software (β version), T 1/2, T lag, GEC and the regression-estimated constants (β and κ) were calculated. The differences in the parameters measured at two time-points were analyzed using Wilcoxon's signed-rank test. There was a significant difference in the calculated parameter β. No significant differences in the calculated parameters T 1/2, T lag, GEC or κ were observed between the test meal with ramosetron group and the test meal alone group. This study showed that ramosetron pre-treatment enhances the early gastric emptying of liquid nutrients.

Ramosetron Does Not Reduce the Analgesic Efficacy of Tramadol after Gynecological Laparoscopic Surgery.

Background The effect of ramosetron on the analgesic action of tramadol is not well known when ramosetron is added to intravenous-tramadol patient-controlled analgesia (PCA) and infused continuously. The aim of this randomized noninferiority study was to evaluate the effects of ramosetron on the analgesic action of tramadol when it is administered simultaneously in women undergoing laparoscopic gynecology who are receiving tramadol via IV PCA. Method This study used a prospective, randomized, controlled, noninferiority clinical trial design and compared the analgesic effect of tramadol plus ramosetron with that of tramadol only. A total of 110 postoperative patients, who were using IV PCA tramadol, were randomly assigned either to a group receiving ramosetron (group R, n=49) or to a group that received the same volume of normal saline continuously (group N, n=51). Observation time points for cumulative tramadol consumption were the first hour, and every 4 h up to 12 h and then 24 h after surgery. Pain intensity at rest and during movement, coughing, and nausea scores, the analgesic and antiemetic doses used, side effects, and patient satisfaction were evaluated 1 and 24 h after surgery. Results Groups R and N received, respectively, 88 ± 55 vs. 79 ± 42 mg tramadol (P=0.511) after 1 h, 211 ± 122 vs. 198 ± 109 mg cumulative tramadol (P=0.610) after 4 h, 244 ± 150 vs. 231 ± 134 mg cumulative tramadol (P= 0.793) after 8 h, 250 ± 156 vs. 247 ± 153 mg cumulative tramadol (P=0.972) after 12 h, and 294 ± 190 vs. 284 ± 178 mg cumulative tramadol (P=0.791) after 24 h, postsurgery. Tramadol plus ramosetron was shown to be not significantly inferior to tramadol alone in alleviating the postoperative pain. Conclusions The analgesic effect of tramadol combined with ramosetron was found to be noninferior to tramadol alone for postoperative PCA after laparoscopic gynecologic surgery.

COMPARATIVE STUDY BETWEEN INTRAVENOUS RAMOSETRON AND DEXAMETHASONE AS PRE-TREATMENT TO ATTENUATE PAIN DURING INTRAVENOUS PROPOFOL INJECTION

Background: Propofol as an induction agent has disadvantage of pain on intravenous injection (IV). Objective: The aim of this study was to compare the efficacy of ramosetron and dexamethasone as a pretreatment drug for attenuation of pain due to propofol injection. Methods: This randomized comparative study was conducted at a tertiary care hospital in Eastern India, over a period of one year (March 2016-February 2017). Total 90 American Society of Anesthesiologists (ASA) grade I and II patients were randomly assigned into three groups (30 in each). Group R received 2 ml (0.3mg) of ramosetron, Group D received 2 ml (0.1mg/kg) of dexamethasone, and Group N received 2 ml of 0.9% normal saline. Venous drainage was occluded by using a tourniquet in mid-forearm before injecting the pre-treatment solution and released after 1 min and then 2 ml of propofol was injected over 5 sec. Patients were observed and questioned 15 sec later, if they had pain in the arm or discomfort during drug injection. The pain was scored on a four-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. Pearson’s Chi Square test/Fisher's Exact Test and Mann-Whitney U test/Kruskal Wallis Test were used to analyze the results. Results: The overall incidence of pain was 90% in the saline group, 17% in the ramosetron group and 10% in the dexamethasone group. The intensity of pain was significantly less in patients receiving ramosetron and dexamethasone than those receiving saline (P &lt; 0.05). Haemodynamic parameters like heart rate (HR) and mean blood pressure (MBP) were recorded at different points of time. No significant inter group differences in MBP and HR were noted at any point of time. Conclusion: Pre-treatment with intravenous ramosetron and dexamethasone both lead to relief of pain on injection of IV propofol without any significant difference between their effects.

Scheduled injection of ramosetron for prevention of nausea and vomiting following single-port access total laparoscopic hysterectomy: a prospective randomized study.

ObjectiveThe purpose of this study was to evaluate the effectiveness of scheduled ramosetron injections for controlling postoperative nausea and vomiting (PONV) after single-port access total laparoscopic hysterectomy (SPA-TLH).MethodsNinety patients who underwent SPA-TLH at the Korean National Health Insurance Service Ilsan Hospital between June 2013 and July 2014 were enrolled in this prospective, randomized, double-blinded, placebo-controlled study. The patients were divided into 2 groups as follows: the ramosetron group (0.3 mg intravenously [IV]; n=45) and the placebo group (normal saline IV; n=45). Both groups received their respective injections 12 and 24 hours post surgery. The incidence and severity of PONV (numerical rating scale, 0–10), and the use of rescue antiemetics post surgery were evaluated.ResultsDemographic and perioperative statistically significant differences were not observed between the 2 groups. The incidence of PONV in the ramosetron and placebo groups was 46.7% and 51.1%, respectively (P=0.51). We found significant differences in the severity of PONV between the 24- to 48-hour postoperative periods in both groups (ramosetron group, P=0.04 and placebo group, P=0.03). The use of rescue antiemetics was significantly lower in the ramosetron group than in the placebo group (P=0.02).ConclusionAfter general anesthesia, scheduled injections of ramosetron 12 and 24 hours after SPA-TLH reduced the severity of PONV and the use of rescue antiemetics. Administration of ramosetron can be considered not only immediately after SPA-TLH but also during the first 24-hour recovery period.Trial RegistrationClinicalTrials.gov Identifier: NCT 02011659

Nephrotoxicity Evaluation on Cisplatin Combined with 5-HT3 Receptor Antagonists: A Retrospective Study

Objective 5-HT3 receptor antagonist (ondansetron) has been reported to have nephrotoxic effect when combined with cisplatin in mice; however, little evidence exists in explaining its nephrotoxic effects on patients. The aim of this present study was to investigate whether 5-HT3 receptor antagonist could enhance or aggravate the incidence of cisplatin-induced nephrotoxicity in patients. Methods We retrospectively reviewed 600 tumor patients which were treated with cisplatin (⩾60 mg/m2) as a first-time chemotherapy and combined with 5-HT3 receptor antagonist (i.e., ondansetron, tropisetron, or ramosetron, each kind of 5-HT3 receptor antagonist contains 200 cases) between January 2010 and December 2015. Cisplatin dosing, the baseline creatinine clearance, and other independent risk factors such as patient's age, sex, PS score, and weight associated with nephrotoxicity were evaluated in a multivariable model. Results The incidence of Grade ⩾ 2 serum creatinine elevation in cisplatin + ondansetron group was significantly higher than cisplatin + tropisetron group (P = 0.04), but no significant difference was found between cisplatin + ondansetron group and cisplatin + ramosetron group (P = 0.3). It was also found that cisplatin dosage and tumor type were independent risk factors in the development of nephrotoxicity. Conclusion Higher cisplatin dosage and regular use of ondansetron combined with cisplatin are more likely to increase the incidence of nephrotoxicity; tropisetron showed the relatively mild effect on kidney function, suggesting that tropisetron is a preferable alternative in the process of cisplatin chemotherapy.

Comparison of ramosetron and ondansetron for the treatment of established postoperative nausea and vomiting after laparoscopic surgery: a prospective, randomized, double-blinded multicenter trial.

BackgroundPostoperative nausea and vomiting (PONV) is a common complication after surgery, which increases physical and psychological discomfort and delays recovery. The aim of this study was to test the hypothesis that ramosetron is comparable to ondansetron for the treatment of established PONV after laparoscopic surgery using a prospective, randomized, double-blinded, noninferiority study.MethodsPatients who had at least two risk factors of PONV and underwent laparoscopic surgery under general anesthesia were assessed for eligibility. Patients who developed PONV within the first 2 h after anesthesia received ondansetron (4 mg) or ramosetron (0.3 mg) intravenously in a randomized double-blind manner. Patients were then observed for 24 h after drug administration. The incidence of nausea and vomiting, severity of nausea, rescue antiemetic necessity, and adverse effects at 0–2 or 2–24 h after drug administration was evaluated. The primary endpoint was the rate of patients exhibiting a complete response, defined as no emesis and no further rescue antiemetic medication for 24 h after drug administration.ResultsAmong the 583 patients, 210 (36.0%) developed PONV and were randomized to either the ondansetron (n=105) or ramosetron (n=105) group. Patient’s characteristics were similar between the groups. The complete response rate was 44.1% in the ondansetron group and 52.9% in the ramosetron group after 24 h of initial antiemetic administration. The incidence of adverse events was not different between the groups.ConclusionWe found evidence to support the noninferiority of ramosetron (0.3 mg) compared to ondansetron (4 mg) for the treatment of established PONV in moderate to high-risk patients undergoing laparoscopic surgery.

Ramosetron for the treatment of irritable bowel syndrome with diarrhea: a systematic review and meta-analysis of randomized controlled trials

BackgroundRamosetron is a potent and selective serotonin type 3 receptor antagonist. This meta-analysis aimed to analyze the efficacy and safety of ramosetron for irritable bowel syndrome with diarrhea (IBS-D).MethodsPubmed, MEDLINE, EMBASE and the Cochrane Library were searched for randomized controlled trials investigating the efficacy and safety of ramosetron for IBS-D. Risk of bias was assessed as described in the Cochrane handbook. A random effects model was used to calculate the effects of ramosetron vs placebo on symptomatic improvements, including relief of overall IBS symptoms, relief of abdominal discomfort/pain, improvement in abnormal bowel habits, and improvement in stool consistency, expressed as pooled relative risks (RRs) with 95% confidence interval (CI). Adverse events data were also summarized with RRs.ResultsFour randomized controlled trials involving 1623 participants were included. Compared with placebo, ramosetron could lead to relief of overall IBS symptoms (RR 1.70; 95%CI 1.48, 1.95), relief of abdominal discomfort/pain (RR 1.41; 95%CI, 1.24, 1.59), improvement in abnormal bowel habits (RR 1.72; 95%CI, 1.50, 1.98) and improvement in stool consistency (RR 1.71; 95%CI 1.40, 2.08). Ramosetron could lead to relief of overall IBS symptoms in both male and female patients (RR; 95%CI: 1.94; 1.58, 2.38 and 1.49; 1.25, 1.79). The RR (95%CI) for reported adverse events of ramosetron vs placebo was 1.10 (0.97, 1.26) across all studies. No serious adverse events (e.g., ischemic colitis) were reported. The incidences of hard stool and constipation were higher in ramosetron group compared with placebo group (RR; 95%CI: 4.74; 3.00, 7.51 and 2.53; 1.57, 4.10, respectively).ConclusionsRamosetron had beneficial effects to both male and female IBS-D patients. Treatment with ramosetron could cause more hard stool and constipation, without severe adverse events.

Randomized, placebo-controlled, phase IV pilot study of ramosetron to evaluate the co-primary end points in male patients with irritable bowel syndrome with diarrhea

BackgroundGlobal assessment allows patients to assess improvement in multiple irritable bowel syndrome (IBS) symptoms. However, it was deemed important to assess “clinically meaningful improvements, focusing on the patient’s chief complaint and the severity of major IBS symptoms” in addition to global assessment to show how ramosetron is effective for individual IBS symptoms. This is a pilot study to explore clinical endpoints focusing on the chief complaint of patients with IBS with diarrhea (IBS-D).MethodsThe same database was used in a previously reported post-marketing phase IV, randomized placebo-controlled pilot trial in male patients with IBS-D. The hypothesis is completely different from that of the other study. Patients with IBS-D diagnosed according to Rome III criteria were given either 5 μg of ramosetron (n = 47) or placebo (n = 51) once daily for 12 weeks after a one-week baseline period. To explore and examine endpoints that allow evaluation of “clinically meaningful improvements focusing on the patient’s chief complaint,” the chief complaint and its relief by this study drug were assessed in this exploratory study.ResultsRates of patients with abdominal pain/discomfort, stool form and stool frequency which patients had as a chief complaint before administration were 34.0, 19.1 and 25.5%, respectively, in the ramosetron 5 μg group and 42.0, 18.0, and 20.0% in the placebo group. Responder rates for improvement in symptoms of the chief complaint that patients had before administration were 53.2% in the ramosetron 5 μg group and 42.0% in the placebo group at the last point. The greatest symptomatic improvement in the chief complaint in the ramosetron 5 μg group compared to the placebo group was shown with respect to stool consistency. Bristol Stool Form Scale (BSFS) scores were significantly lower in the ramosetron group than in the placebo group (4.36 ± 1.195 vs 4.85 ± 0.890 at the last point, P = 0.027) throughout the treatment period, except at week 6.ConclusionsRamosetron acted most effectively on stool consistency. Improvement in stool consistency is considered to be a clinically meaningful endpoint in showing how ramosetron was effective for individual IBS symptoms. (Clinicaltrials.gov ID: NCT00918411. Registered 9 June 2009).