Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study
Abstract Background The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU). Methods This was a multicenter, randomized, double-blinded, fenta...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Intensive Care |
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| Online Access: | https://doi.org/10.1186/s40560-023-00698-9 |
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| author | Matsuyuki Doi Naoki Takahashi Rumi Nojiri Takehiko Hiraoka Yusuke Kishimoto Shinichi Inoue Nobuyo Oya |
| author_facet | Matsuyuki Doi Naoki Takahashi Rumi Nojiri Takehiko Hiraoka Yusuke Kishimoto Shinichi Inoue Nobuyo Oya |
| author_sort | Matsuyuki Doi |
| collection | DOAJ |
| description | Abstract Background The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU). Methods This was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients. Results The proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, − 0.8–5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil. Conclusions Remifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU. Trial registration: Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954 . |
| first_indexed | 2024-03-10T22:14:22Z |
| format | Article |
| id | doaj.art-7932256378384001a0ca3c90c4e01523 |
| institution | Directory Open Access Journal |
| issn | 2052-0492 |
| language | English |
| last_indexed | 2024-03-10T22:14:22Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
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| series | Journal of Intensive Care |
| spelling | doaj.art-7932256378384001a0ca3c90c4e015232023-11-19T12:30:29ZengBMCJournal of Intensive Care2052-04922023-11-0111111310.1186/s40560-023-00698-9Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 studyMatsuyuki Doi0Naoki Takahashi1Rumi Nojiri2Takehiko Hiraoka3Yusuke Kishimoto4Shinichi Inoue5Nobuyo Oya6Department of Anesthesiology and Intensive Care Medicine, Hamamatsu University School of MedicineClinical Development Department, Maruishi Pharmaceutical Co., Ltd.Clinical Development Department, Maruishi Pharmaceutical Co., Ltd.Clinical Development Department, Maruishi Pharmaceutical Co., Ltd.Clinical Development Department, Maruishi Pharmaceutical Co., Ltd.Clinical Development Department, Maruishi Pharmaceutical Co., Ltd.Clinical Development Department, Maruishi Pharmaceutical Co., Ltd.Abstract Background The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU). Methods This was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients. Results The proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, − 0.8–5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil. Conclusions Remifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU. Trial registration: Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954 .https://doi.org/10.1186/s40560-023-00698-9FentanylIntensive care unitMechanical ventilationPain managementRemifentanil |
| spellingShingle | Matsuyuki Doi Naoki Takahashi Rumi Nojiri Takehiko Hiraoka Yusuke Kishimoto Shinichi Inoue Nobuyo Oya Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study Journal of Intensive Care Fentanyl Intensive care unit Mechanical ventilation Pain management Remifentanil |
| title | Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study |
| title_full | Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study |
| title_fullStr | Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study |
| title_full_unstemmed | Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study |
| title_short | Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study |
| title_sort | efficacy safety and pharmacokinetics of mr13a11a a generic of remifentanil for pain management of japanese patients in the intensive care unit a double blinded fentanyl controlled randomized non inferiority phase 3 study |
| topic | Fentanyl Intensive care unit Mechanical ventilation Pain management Remifentanil |
| url | https://doi.org/10.1186/s40560-023-00698-9 |
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