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

NCT02811991 | Completed Phase 2

• 1 other identifier: HR-DYXAJF-Ⅲ
• Study Type: interventional
• Target: 348
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Post-operative Analgesia

Keywords

paracetamol; post-operative analgesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

Experimental:Paracetamol Injection

ACTIVE COMPARATOR

325mg(32.5mL)or 500mg(50mL) iv q6h according to assignment

Drug: Paracetamol injection; Drug: Morhpine PCA

Placebo:Normal Saline Injcetion

PLACEBO COMPARATOR

32.5mLor 50mL iv q6h according to assignment.

Drug: Normal Saline injection; Drug: Morhpine PCA

Interventions

Paracetamol injection DRUG

325mg(32.5mL) or 500mg(50mL) iv q6h,4 doses in 24h.Infushion time≥15min.

Experimental:Paracetamol Injection

Normal Saline injection DRUG

32.5mL or 50mL iv q6h,4 doses in 24h.Infushion time≥15min.

Placebo:Normal Saline Injcetion

Morhpine PCA DRUG

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.

Experimental:Paracetamol Injection; Placebo:Normal Saline Injcetion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• kg/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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (16)

Beijing Chao-Yang Hospital

Beijing, Beijing Municipality, 100020, China

Location

Beijing Friendship Hospital

Beijing, Beijing Municipality, 100050, China

Location

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

Location

The South West Hospital

Chongqing, Chongqing Municipality, 400042, China

Location

Fuzhou General Hospital of Nanjing Millitary Command

Fuzhou, Fujian, 350025, China

Location

Liuzhou General Hospital

Liuchow, Guangxi, 545006, China

Location

Guizhou Provincial People's Hospital

Guiyang, Guizhou, 551100, China

Location

The Third Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050051, China

Location

the Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

No.1 People's Hospital of Chenzhou City

Chenzhou, Hunan, 423000, China

Location

Affiliated Hospital,Jiangnan University

Wuxi, Jiangsu, 214062, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Tongji Hospital Affiliated to Tongji University

Shanghai, Shanghai Municipality, 200065, China

Location

West China Hospital

Chengdu, Sichuan, 610041, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

Ningbo No.2 Hospital

Ningbo, Zhejiang, 315010, China

Location

Related Publications (1)

• 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.

  PMID: 35935863 DERIVED

MeSH Terms

Interventions

Acetaminophen; Saline Solution

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Fei Liu, Ph.D

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: June 23, 2016
• Study Start: June 1, 2016
• Primary Completion: September 14, 2018
• Study Completion: May 1, 2019
• Last Updated: November 5, 2019

Record last verified: 2019-11

Locations

CN (16)