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

NCT ID: NCT04199572

Last Updated: 2023-03-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-16

Study Completion Date

2023-02-21

Brief Summary

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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

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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.

Conditions

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Musculoskeletal Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Combination 1- Diclofenac Placebo Paracetamol (Oral) Combination 2- Diclofenac Paracetamol (IV) Placebo Combination 3- Diclofenac Placebo Placebo
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
The physicians, participants, nurses and the outcome assessor will all be blinded to the intervention. The trial packets will be prepared containing the active drugs and placebos.

Study Groups

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Diclofenac and Oral Paracetamol

Diclofenac (75mg intramuscular), Placebo (100ml intravenous Normal Saline), Paracetamol (per oral 1gm)

Group Type EXPERIMENTAL

Diclofenac and Paracetamol

Intervention Type DRUG

analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo

Diclofenac and IV Paracetamol

Diclofenac (75mg intramuscular), Paracetamol (intravenous1gm in 100ml solution), Placebo (sugar tablets)

Group Type EXPERIMENTAL

Diclofenac and Paracetamol

Intervention Type DRUG

analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo

Diclofenac and Placebo

Diclofenac (75mg intramuscular),Placebo (100ml intravenous Normal Saline),Placebo (sugar tablets)

Group Type EXPERIMENTAL

Diclofenac and Paracetamol

Intervention Type DRUG

analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo

Interventions

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Diclofenac and Paracetamol

analgesic effect of diclofenac along with either Oral versus Intravenous paracetamol versus placebo

Intervention Type DRUG

Other Intervention Names

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Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hamad Medical Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Dr. Isma Qureshi

Academic Research Associate

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Hamad Medical Corporation

Doha, , Qatar

Site Status

Countries

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Qatar

References

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Tramer MR, Williams JE, Carroll D, Wiffen PJ, Moore RA, McQuay HJ. Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: a qualitative systematic review. Acta Anaesthesiol Scand. 1998 Jan;42(1):71-9. doi: 10.1111/j.1399-6576.1998.tb05083.x.

Reference Type BACKGROUND
PMID: 9527748 (View on PubMed)

Khalili G, Janghorbani M, Saryazdi H, Emaminejad A. Effect of preemptive and preventive acetaminophen on postoperative pain score: a randomized, double-blind trial of patients undergoing lower extremity surgery. J Clin Anesth. 2013 May;25(3):188-92. doi: 10.1016/j.jclinane.2012.09.004. Epub 2013 Apr 6.

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Aarons L, Ogungbenro K. Optimal design of pharmacokinetic studies. Basic Clin Pharmacol Toxicol. 2010 Mar;106(3):250-5. doi: 10.1111/j.1742-7843.2009.00533.x. Epub 2010 Jan 20.

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Krug EG, Sharma GK, Lozano R. The global burden of injuries. Am J Public Health. 2000 Apr;90(4):523-6. doi: 10.2105/ajph.90.4.523.

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Macintyre PE, Schug SA, Scott DA. Acute pain management: the evidence grows. Med J Aust. 2006 Feb 6;184(3):101-2. doi: 10.5694/j.1326-5377.2006.tb00144.x.

Reference Type RESULT
PMID: 16460291 (View on PubMed)

Tveita T, Thoner J, Klepstad P, Dale O, Jystad A, Borchgrevink PC. A controlled comparison between single doses of intravenous and intramuscular morphine with respect to analgesic effects and patient safety. Acta Anaesthesiol Scand. 2008 Aug;52(7):920-5. doi: 10.1111/j.1399-6576.2008.01608.x.

Reference Type RESULT
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Tuomilehto H, Kokki H. Parenteral ketoprofen for pain management after adenoidectomy: comparison of intravenous and intramuscular routes of administration. Acta Anaesthesiol Scand. 2002 Feb;46(2):184-9. doi: 10.1034/j.1399-6576.2002.460211.x.

Reference Type RESULT
PMID: 11942868 (View on PubMed)

Hindle A, Spedding R. Managing acute renal colic. Intramuscular diclofenac should be avoided. BMJ. 2003 Mar 1;326(7387):502. doi: 10.1136/bmj.326.7387.502. No abstract available.

Reference Type RESULT
PMID: 12609956 (View on PubMed)

Wright PJ, English PJ, Hungin AP, Marsden SN. Managing acute renal colic across the primary-secondary care interface: a pathway of care based on evidence and consensus. BMJ. 2002 Dec 14;325(7377):1408-12. doi: 10.1136/bmj.325.7377.1408. No abstract available.

Reference Type RESULT
PMID: 12480861 (View on PubMed)

Moran CP, Courtney AE. Managing acute and chronic renal stone disease. Practitioner. 2016 Feb;260(1790):17-20, 2-3.

Reference Type RESULT
PMID: 27032222 (View on PubMed)

Pathan SA, Mitra B, Straney LD, Afzal MS, Anjum S, Shukla D, Morley K, Al Hilli SA, Al Rumaihi K, Thomas SH, Cameron PA. Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial. Lancet. 2016 May 14;387(10032):1999-2007. doi: 10.1016/S0140-6736(16)00652-8. Epub 2016 Mar 16.

Reference Type RESULT
PMID: 26993881 (View on PubMed)

Babl FE, Theophilos T, Palmer GM. Is there a role for intravenous acetaminophen in pediatric emergency departments? Pediatr Emerg Care. 2011 Jun;27(6):496-9. doi: 10.1097/PEC.0b013e31821d8629.

Reference Type RESULT
PMID: 21629146 (View on PubMed)

Serinken M, Eken C, Turkcuer I, Elicabuk H, Uyanik E, Schultz CH. Intravenous paracetamol versus morphine for renal colic in the emergency department: a randomised double-blind controlled trial. Emerg Med J. 2012 Nov;29(11):902-5. doi: 10.1136/emermed-2011-200165. Epub 2011 Dec 20.

Reference Type RESULT
PMID: 22186009 (View on PubMed)

Craig M, Jeavons R, Probert J, Benger J. Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department. Emerg Med J. 2012 Jan;29(1):37-9. doi: 10.1136/emj.2010.104687. Epub 2011 Mar 1.

Reference Type RESULT
PMID: 21362724 (View on PubMed)

Bektas F, Eken C, Karadeniz O, Goksu E, Cubuk M, Cete Y. Intravenous paracetamol or morphine for the treatment of renal colic: a randomized, placebo-controlled trial. Ann Emerg Med. 2009 Oct;54(4):568-74. doi: 10.1016/j.annemergmed.2009.06.501. Epub 2009 Jul 31.

Reference Type RESULT
PMID: 19647342 (View on PubMed)

Grissa MH, Claessens YE, Bouida W, Boubaker H, Boudhib L, Kerkeni W, Boukef R, Nouira S. Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial. Am J Emerg Med. 2011 Feb;29(2):203-6. doi: 10.1016/j.ajem.2009.09.019. Epub 2010 Oct 8.

Reference Type RESULT
PMID: 20934829 (View on PubMed)

Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. 2005 Apr;102(4):822-31. doi: 10.1097/00000542-200504000-00019.

Reference Type RESULT
PMID: 15791113 (View on PubMed)

Olonisakin RP, Amanor-Boadu SD, Akinyemi AO. Morphine-sparing effect of intravenous paracetamol for post operative pain management following gynaecological surgery. Afr J Med Med Sci. 2012 Dec;41(4):429-36.

Reference Type RESULT
PMID: 23672109 (View on PubMed)

Other Identifiers

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IRGC-04-NI-17-099

Identifier Type: -

Identifier Source: org_study_id

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