A PhaseⅡ/ Ⅲ Seamless Study to Evaluate Efficacy and Safety of Paracetamol Injection as Adjuvant to Morphine-based Postoperative Analgesia

A PhaseⅡ/ Ⅲ Seamless Study to Evaluate Efficacy and Safety of Paracetamol Injection as Adjuvant to Morphine-based Postoperative Analgesia-Multicentered, Randomized, Double-blind, Placebo-controlled Clinical Trial

Paracetamol,a classical analgesic agent,constitutes an essential component of multi-modal analgesia. This medication is generally safe, well tolerated and effective within recommended daily dose.The purpose of the study is to evaluate the efficacy and safety of Paracetamol Injection as adjuvant to morphine-based post-operative analgesia, as well as to explore the reasonable dosage of paracetamol among Chinese population under above-mentioned circumstance.

Study Overview

• Status: Completed
• Conditions: Post-operative Analgesia
• Intervention / Treatment: Drug: Paracetamol injection; Drug: Morhpine PCA; Drug: Normal Saline injection

• Study Type: Interventional
• Enrollment (Actual): 348
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • The South West Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Fuzhou General Hospital of Nanjing Millitary Command
  • Guangxi
    • Liuzhou, Guangxi, China, 545006
      • Liuzhou General Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 551100
      • Guizhou Provincial People's Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The Third Hospital of Hebei Medical University
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
    • Chenzhou, Hunan, China, 423000
      • No.1 People's Hospital of Chenzhou City
  • Jiangsu
    • Wuxi, Jiangsu, China, 214062
      • Affiliated Hospital,Jiangnan University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Tongji hospital affiliated to tongji university
  • Sichuan
    • Chendu, Sichuan, China, 610041
      • West China Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Ningbo, Zhejiang, China, 315010
      • Ningbo No.2 Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged from 18 to 70 years inclusively, male or female;
• Patients scheduled for open abdominal surgery(such as gall bladder, lower abdominal investigative surgery), gynecologic surgery(such as trans-abdominal hysterectomy), orthopedic surgery(such as replacement and reconstruction of knee, hip or shoulder joint), with anticipated need for post-operative iv. morphine analgesia≥24h;
• 18kg/m2≤BMI≤30 kg/m2;
• Classified as ASA risk class I, II according to the American Society of Anesthesiologists;
• Able to understand the study procedures and the use of the pain scales, able to operate a patient controlled analgesia (PCA) device and to communicate meaningfully with the study observer and staff;
• Patients free of any contraindication to the study drugs, morphine and to the standardized anesthesia protocol;
• Clearly understand the procedure of study, voluntarily participate and provided written consent form.

Exclusion Criteria:

• Impaired liver function (ALT and/or AST > 2 x upper limit of normal range, or TBIL≥1.5 x upper limit of normal range);
• Impaired renal function(Serum Creatinine >176μmoL/L), or undergoing dialysis within 28 days before surgery;
• Patients at high risk for bleeding, including congenital hemorrhagic disease(such as Hemophilia), Thrombocytopenia(CBC PLT<30×109/L), Qualitative Plateletdefects(such as ITP, DIC, congenital abonormal platelet), or clinically significant active bleeding;
• Abnormal resting ECG, judged as not eligible for entry by investigator;
• Hypertensive patients not achieving satisfactory BP control under hypertensive medication(Sitting SBP≥160mm Hg, and/or DBP≥105mm Hg during screen period);
• Sitting SBP≤90mm Hg during screening period;
• Diabetic Patients not achieving satisfactory blood glucose control(FBG≥11.1moL/L during screening period);
• Known history of bronchial asthma, pulmonary heart disease or heart failure;
• Participation in other trials within 30 days;
• Pregnant women or women in lactation;
• Patients not eligible due to other reasons judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental:Paracetamol Injection; 325mg(32.5mL)or 500mg(50mL) iv q6h according to assignment	Drug: Paracetamol injection; 325mg(32.5mL) or 500mg(50mL) iv q6h,4 doses in 24h.Infushion time≥15min.; Drug: Morhpine PCA; Morphine PCA will be connected upon the first dose of study drug(roughly 30min prior to the completion of would suture). Morphine PCA is set as follows:1mg bolus every 5min with background infusion of 0.25mg/h and maximal dose<25mg/4h.
Placebo Comparator: Placebo:Normal Saline Injcetion; 32.5mLor 50mL iv q6h according to assignment.	Drug: Morhpine PCA; Morphine PCA will be connected upon the first dose of study drug(roughly 30min prior to the completion of would suture). Morphine PCA is set as follows:1mg bolus every 5min with background infusion of 0.25mg/h and maximal dose<25mg/4h.; Drug: Normal Saline injection; 32.5mL or 50mL iv q6h,4 doses in 24h.Infushion time≥15min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total morphine use in 24 hours	Total morhpine use(including PCA and emergency morphine use)in 24 hours.	24h after the 1st dose of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Pain Intensity VAS AUC(0-24h) at rest	0-24h PI VAS AUC(mesured at 1h、3h、6h、12h、24h after the 1st dose of study drug)
Pain Intensity VAS AUC(0-24h) at movement	0-24h PI VAS AUC(mesured at 1h、3h、6h、12h、24h after the 1st dose of study drug)
Incidence of mophine-related ADR	0-24h after the 1st dose of study drug

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Fei Liu, Ph.D, West China Hospital

Publications and helpful links

General Publications

• Yin F, Ma W, Liu Q, Xiong LL, Wang TH, Li Q, Liu F. Efficacy and safety of intravenous acetaminophen (2 g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial. Front Pharmacol. 2022 Jul 22;13:909572. doi: 10.3389/fphar.2022.909572. eCollection 2022.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): September 14, 2018
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: June 21, 2016
• First Posted (Estimate): June 23, 2016

Study Record Updates

• Last Update Posted (Actual): November 5, 2019
• Last Update Submitted That Met QC Criteria: November 3, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: paracetamol; post-operative analgesia
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Agnosia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: HR-DYXAJF-Ⅲ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided