CTRI/2023/05/052794 [Registered on: 17/05/2023] Trial Registered Prospectively
Last Modified On:
15/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A clinical trial to compare the effect of paracetamol 1000 mg/4 ml and paracetamol 1000 mg/100 ml in patients having pain after surgery.
Scientific Title of Study
A multicentre, prospective, randomized, open label, active controlled, clinical trial evaluating the efficacy and safety of Paracetamol 1000 mg/4 ml intravenous bolus injection vs Paracetamol intravenous infusion 1% w/v (100 ml) for the treatment of post-operative pain
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CT/55/01/22 version 01 dated 13.07.2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Institutional Ethics Committee, Lokmanya Medical Research Centre
Approved
Institutional Ethics Committee-KIMS
Submittted/Under Review
IPGME and R Research Oversight Committee
Approved
LPR Ethics Committees
Approved
Parth Hospital Ethics Committee
Approved
Riddhi Medical Nursing Home
Approved
Sir Ganga Ram Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: O||Medical and Surgical,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Kabimol (Paracetamol Infusion 1% w/v) 100 ml of Fresenius Kabi India Pvt Ltd.
Reference Drug will be given every six hours for 24 hours (total four doses).
Intervention
Paracetamol 1000 mg/4 ml intravenous bolus injection (Mfg. by Troikaa Pharmaceuticals Ltd).
Test drug will be given every six hours for 24 hours (total four doses).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
70.00 Year(s)
Gender
Both
Details
1. Patients of either gender in the age group of 18-70 years.
2. Patients with body weight more than 50 kg.
3. Patients scheduled for elective unilateral or bilateral, primary or uncomplicated secondary total replacement of hip or knee or abdominal surgery performed according to the standard technique used in each study site.
4. Patient with physical status I or II, as per American Society of Anaesthesiologists Physical Status Classification (Annexure - I).
5. Patients willing to give written informed consent prior to participation in the study.
6. Patients who require post-operative hospitalization for at least 48 hours.
7. Able to understand the study procedures and the use of the pain scales and to communicate meaningfully with the study observer and staff.
8. Patient requires surgery performed under general, spinal or epidural anaesthesia.
9. Patient free of any contra-indication to the study drugs and the rescue medication.
10. Patient free of other painful physical conditions which might confound quantifying postoperative pain.
11. The female subjects who are of non-childbearing potential (or of childbearing potential, and who have a negative urine pregnancy test at screening).
Post-Operative Day 1 Randomization Criterion:
Patient having postoperative pain intensity of following scale on the morning of post operation Day 1
1. ≥40 mm at rest on a 100 mm Visual Analogue Scale (VAS).
ExclusionCriteria
Details
1. Patients with known hypersensitivity or contra indication to paracetamol.
2. Patient with known or suspected history of alcohol or drug abuse.
3. Patient with psychiatric disease or medical conditions which in the opinion of the investigator might invalidate patient ability to communicate with the investigator or to comply with the study procedures.
4. Any abdominal laparoscopic surgeries in which bariatric procedures including gastric bypass or gastric banding, exploratory procedures in which no visceral dissection was performed, and procedures with minimal visceral dissection, such as laparoscopic sterilization.
5. Patient scheduled for early re-intervention or re-instrumentation, i.e. within 30 days of the initial procedure or less.
6. Patients with serum creatinine more than 2.5 times of the upper limit of normal value.
7. Patients with elevated liver enzymes (SGOT, SGPT and Total Bilirubin) more than 2 times of the upper limit of normal value.
8. Patient with active hepatic disease, evidence of clinically significant liver disease, or other condition (e.g., alcoholism, cirrhosis, or hepatitis) that suggested the potential for an increased susceptibility to hepatic toxicity with study medication exposure.
9. Respiratory insufficiency or severe cardiac insufficiency not stabilized by therapy.
10. Patients with present history of hypotension or shock.
11. Patients with raised intracranial pressure or convulsions.
12. Patients with present history of peptic ulcers and/or gastrointestinal bleeding.
13. Pregnant and/or lactating women.
14. Patient has participated in another clinical study (investigational or marketed product) within 30 days prior to screening.
15. Patients, for any reason not considered to be suitable candidate by the investigator.
16. Patient who was taking any concomitant treatments (i.e. sedatives, hypnotics, anxiolytics, anti-depressant drugs, tranquilizers) which could potentially confound the quantification of analgesia.
17. Patient treated with MAO inhibitors or whose treatment with these had been stopped less than 10 days prior to surgery; patient treated with corticosteroids or whose treatment with these had been stopped less than 7 days prior surgery.
18. Patient treated with microsomal enzyme inducers such as barbiturates, isoniazid, anticonvulsants or zidovudine.
Postoperative Eligibility Exclusion Criteria:
A subject will not be eligible for entry if any of the following criteria will met after surgery:
1. Subject undergoes any surgery other than the planned surgery or had intraoperative or postoperative complications that, in the view of the investigator, made study participation inadvisable.
2. Patient who had taken NSAIDs / any other analgesic drug within 8 hours (48 h for long acting NSAIDs) prior to administration of the study medications.
3. Patient receiving epidural or intrathecal opioids or local anaesthetics for postoperative pain control.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Pain intensity difference on VAS (PIDvas) at 1 hr from baseline
1 hr
Secondary Outcome
Outcome
TimePoints
Pain intensity difference on VAS (PIDvas) from baseline.
Peak pain scores: MAXPID (maximum pain intensity difference from baseline on VAS), MAXPR (maximum pain relief), and MAXPRID (maximum time-specific sum of PIDcat and PR (PRID))
over 6 hr
Time to peak scores (MAXPID, MAXPR, MAXPRID)
over 6 hr
Summation of pain scores: TOTPAR (Time-weighted summation of pain relief scores by area under the PR), SPIDvas (Time-weighted summation of pain scores by area under the PIDvas), SPIDcat (Time-weighted summation of pain scores by area under the PIDcat), and SPRID (Time-weighted Sum of Pain Relief (PR) and Pain Intensity Difference (PIDcat)).
Patient global evaluation of satisfaction with study treatment (four-point scale)
6 and 24 hrs
Occurrence of injection site phlebitis will be assesses using Visual Infusion Phlebitis scale
1 hour post each dose.
Vital signs
baseline, one hour after each dose and at 24-hour post first dose
Laboratory investigations
baseline and at the end of study.
Physical examinations
baseline and at the end of study
Treatment emergent adverse events
up to 24 hours
Pain on injection site at the time of injection
at each doses (total four dose every six hours over 24 hours)
Target Sample Size
Total Sample Size="504" Sample Size from India="504" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Troikaa Pharmaceuticals Limited has developed 1g in 4 ml (250 mg/ml) formulation of paracetamol, which is proposed to be, administered as slow IV bolus after diluting it in 16 ml of sterile water for injection. Therefore, administration of this formulation over one day will only increase fluid volume by 80 ml and can be administered safely in patient with volume overload. It will be more convenient than the infusion and will also decrease the cost of therapy.
This is a multicentre, prospective, randomized, open label, active controlled, clinical trial evaluating the efficacy and safety of Paracetamol 1000 mg/4 ml intravenous bolus injection vs Paracetamol intravenous infusion 1% w/v (100 ml) for the treatment of post-operative pain. Adult patients requiring surgery will be screened (within 14 days of receiving study drug treatment) for eligibility based on screening inclusion and exclusion criteria and they will undergo surgery (Day 0) as per investigator’s surgery (surgical procedure, anaesthesia and analgesia) protocol. On the next day morning of the surgery (Day 1), patient eligible as per post-operative day 1 inclusion/exclusion randomization criterion will be randomised in test and reference arms (1:1) to receive study drug treatments. Patient will receive either four intravenous bolus injections over 2 minutes of test product or intravenous infusion over 15 minutes of reference product every 6 hours for 24 hours. After first dose of study drug administration, patients will be evaluated for pain intensity, pain relief, rescue drug requirement and safety parameters at pre-defined time-points till 24 hours post first dose.