Synergistic Effect Of Parenteral Diclofenac And Paracetamol In The Pain Management Of Acute Limb Injuries

Study Overview
=================
Brief Summary
-----------------
Acute limb injury is a common reason to visit an emergency department worldwide. Intense pain related to the injury is always a concern for an emergency physician and requires effective analgesia within the shortest possible time. Non-steroidal anti-inflammatory drugs (NSAIDs), opioids and paracetamol are the commonly used drugs in an emergency department. The choice of analgesia should be established by its efficacy, logistics involved and route of administration. There is good evidence about NSAIDs being the first line analgesia and paracetamol is reported to have the narcotic sparing effect, either alone or as an adjunctive treatment in different settings. The synergistic effect of paracetamol with diclofenac in acute limb injuries related pain management lacks good- quality evidence. Therefore investigators proposed a large, well designed, randomized double-blind trial to develop high-quality evidence. The study aims to assess the efficacy of paracetamol in addition to diclofenac, and compare the difference between oral and intravenous paracetamol administration in acute limb injuries in the emergency department.

Detailed Description
-----------------
Injuries account for a large burden of mortality and morbidity in the state of Qatar and worldwide. Among all the acute injuries, limb injuries are very common. Immense pain of patients on presentation is the matter of concern and requires effective analgesia within the shortest possible time. Most patients with acute limb injuries are treated with, the commonly used analgesics like non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol in the ED. The choice of analgesic should be established by its efficacy, logistics involved, and route of drug administration. Few studies reported that intravenous route is more effective than the intramuscular route, due to its faster absorption and ease of titration. In many ED's intramuscular injectable drugs like NSAIDs are commonly used. Being, readily available and technically faster to administer. There is concern about the use of IM diclofenac in some countries because of possible intramuscular complications; however, most are reported cases in a small proportion (<2 per million doses used). Oral medications are also very commonly used and usually self-administered by the patients with duration of onset being in minutes to an hour. There is good evidence about NSAIDs being the first line analgesic in the management of acute painful conditions such as renal colic. Intramuscular diclofenac is shown to provide safe, effective, and sustained pain relief in addition to being logistically easier to administer. Paracetamol being a centrally acting inhibitor of cyclooxygenases has been reported safe alternative to opioids and equally effective analgesic in the ED with fewer side effects and contraindications. In addition, paracetamol is reported to have the narcotic sparing effect, either alone or as an adjunctive treatment in different settings including post-op pain, cancer pain, and regional anesthesia. The synergistic effect of paracetamol with diclofenac in acute limb injury related- pain management lacks good-quality evidence. Hamad General Hospital Emergency Department (HGH-ED) is the major emergency department (ED) in Doha; Qatar; and offers tertiary level care for emergency conditions. It is also one of the busiest ED's in the world with an annual patient attendance of 0.5 million. Patients with acute limb injuries account for about 25% of the total ED visits. At HGH-ED, intramuscular diclofenac is the analgesia of choice for the management of acute pain of moderate to severe intensity. However, 40-50% of these patients require additional analgesia in the form of opioids or paracetamol. The efficacy of combined analgesia approach, and the difference by route of drug administration in acute ED pain management is yet to be assessed. Therefore investigators proposed a large, well designed, randomized, double- blind trial to develop high-quality evidence. This study aims to assess the efficacy of paracetamol in addition to diclofenac, and compare the difference between oral and intravenous paracetamol administration in acute limb injury pain management in the ED.

Official Title
-----------------
Synergistic Effect Of Parenteral Diclofenac And Paracetamol In The Pain Management Of Acute Limb Injuries

Conditions
-----------------
Musculoskeletal Injury

Intervention / Treatment
-----------------
* Drug: Diclofenac and Paracetamol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years upto 65 years Vitals Stable musculoskeletal limb injury initial pain score of 5 or more on a NRS (numerical rating scale) Exclusion Criteria: Patient received any pain medication prior to 8 hours Allergies to either diclofenac or paracetamol Contraindication to the study drugs CVA Bronchial asthma GI bleeding Renal impairment Asthma Pregnancy and nursing Unstable traumatic patient

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Combination 1- Diclofenac Placebo Paracetamol (Oral) Combination 2- Diclofenac Paracetamol (IV) Placebo Combination 3- Diclofenac Placebo Placebo
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diclofenac and Oral Paracetamol<br>Diclofenac (75mg intramuscular), Placebo (100ml intravenous Normal Saline), Paracetamol (per oral 1gm) | Drug: Diclofenac and Paracetamol<br>* analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo<br>* Other names: Placebo;|
| Experimental: Diclofenac and IV Paracetamol<br>Diclofenac (75mg intramuscular), Paracetamol (intravenous1gm in 100ml solution), Placebo (sugar tablets) | Drug: Diclofenac and Paracetamol<br>* analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo<br>* Other names: Placebo;|
| Experimental: Diclofenac and Placebo<br>Diclofenac (75mg intramuscular),Placebo (100ml intravenous Normal Saline),Placebo (sugar tablets) | Drug: Diclofenac and Paracetamol<br>* analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the difference in mean pain reduction amongst the three groups: numerical rating scale | Pain score on a numerical rating scale (NRS). The scale is a 11 point scale where 0 is no pain and 10 is the worst pain ever. | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the difference in proportion of patients achieving 50% or more pain relief amongst the three groups | Pain score on a numerical rating scale (NRS). The scale is a 11 point scale where 0 is no pain and 10 is the worst pain ever. | 30 minutes | 
| Requirement of rescue analgesia in each group of participants | Pain score on a numerical rating scale (NRS). The scale is a 11 point scale where 0 is no pain and 10 is the worst pain ever. | 30 minutes | 
| The adverse event rate in three groups | any adverse event recorded | 90 minutes | 
| Time to analgesia effect, to achieve 50% reduction, and to NRS <=2 | Pain score on a numerical rating scale (NRS). The scale is a 11 point scale where 0 is no pain and 10 is the worst pain ever. | 90 minutes |