Clinical trial NCT02811991: A PhaseⅡ/ Ⅲ Seamless Study to Evaluate Efficacy and Safety of Paracetamol Injection as Adjuvant to Morphine-based Postoperative Analgesia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Post-operative Analgesia
Keywords: paracetamol
post-operative analgesia
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-06-23
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Total morphine use in 24 hours
timeFrame: 24h after the 1st dose of study drug
Secondary outcomes:
measure: Pain Intensity VAS AUC(0-24h) at rest
timeFrame: 0-24h PI VAS AUC(mesured at 1h、3h、6h、12h、24h after the 1st dose of study drug)
measure: Pain Intensity VAS AUC(0-24h) at movement
timeFrame: 0-24h PI VAS AUC(mesured at 1h、3h、6h、12h、24h after the 1st dose of study drug)
measure: Incidence of mophine-related ADR
timeFrame: 0-24h after the 1st dose of study drug
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Chongqing
country: China
facility: The South West Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Millitary Command
state: Fujian
city: Liuzhou
country: China
facility: Liuzhou General Hospital
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Changsha
country: China
facility: the Third Xiangya Hospital of Central South University
state: Hunan
city: Chenzhou
country: China
facility: No.1 People's Hospital of Chenzhou City
state: Hunan
city: Wuxi
country: China
facility: Affiliated Hospital,Jiangnan University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Tongji Hospital Affiliated to Tongji University
state: Shanghai
city: Chendu
country: China
facility: West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
state: Zhejiang
Study officials:
affiliation: West China Hospital
name: Fei Liu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.