Clinical Trial Comparing Intravenous and Oral Diclofenac and Pharmacokinetics

NCT03472339 | Unknown Phase 4 DMC

• 1 other identifier: 16413/16
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

NSAIDs are commonly used in the management of acute pain; Diclofenac is one from the same class. It is an amino phenyl acetic acid derivative which inhibits prostaglandin biosynthesis to produce analgesic, antipyretic and anti-inflammatory effect. The drug efficacy and safety in acute pain management has been proved by several studies like in renal colic, post and pre-operative pain management, migraines etc. It's also known to have an opioid-sparing effect. Mode of administration is one of the important factors to consider in a busy emergency room. Perception about the route of administration differs among patients. As believed,injectable have rapid onset, easier to titrate, and patients respond better to them as they consider them stronger than oral medication. Number of trials has compared oral and parenteral NSAIDs. Most found no benefit to the parenteral route. Considering the limitations of the previously done studies like small sample size, heterogeneity in the group of patients enrolled, improper blinding and comparing of two different drugs from the same class. Therefore, aim of the study is to conduct a Double blind randomized clinical trial to assess the clinical efficacy and pharmacokinetic parameters of oral diclofenac compared to intramuscular diclofenac in patients with acute limb injury. In this two group double blind randomized clinical trial, the clinical efficacy and pharmacokinetic parameters among the two groups will be assessed. Eligible patients visiting to HGH-ED, age (above 18 years) with acute limb injury, having moderate to severe pain (defined as pain score of \>=4 on Numerical rating scale) will be recruited. With the use of computer generated block randomization, subjects will be allocated to one of the two treatment groups in the ratio of 1:1. Each group will receive either (intramuscular diclofenac / oral placebo) or (oral diclofenac / intramuscular placebo). Among the 300 subjects enrolled for the study, further stratified randomization will be done in order to enroll 20 patients for pharmacokinetic study within the subjects.High-performance liquid chromatography, method will be used for the determination of drug concentration in human plasma, for detailed pharmacokinetics. The pain score will be assessed by using the validated pain scale i.e. Numerical rating scale (NRS). The participants, clinicians and investigators will be masked to treatment assigned and the results will be analyzed by the intention to treat analysis among the two group treatment.

Conditions

Pain Management; Limb Injury

Keywords

Acute limb injury, Diclofenac, pain management

Outcome Measures

Primary Outcomes (2)

• Difference in proportion of patients achieving 50% pain reduction

  The primary outcome is defined as the proportion of patients achieving pain reduction by 50% at 30 minutes following analgesia administration.

  30 mins

• the mean difference in plasma concentration for two drugs

  Cmax - Peak plasma concentration and Time curve

  60 mins

Secondary Outcomes (3)

• proportion of patients achieving pain reduction of >=2 Numerical Rating Scale( which is a numeric scale where respondent selects a whole number from 0 to 10, where 0 means no pain and 10 means worst pain) from the initial score

  at 30 mins

• Rescue analgesia

  after 30 mins

• Adverse events

  2 hours

Study Arms (2)

Group A

EXPERIMENTAL

diclofenac sodium75 mg, intravenously, once

Drug: Diclofenac Sodium

Group B

ACTIVE COMPARATOR

diclofenac sodium 100 mg, orally, once

Drug: Diclofenac Sodium

Interventions

Diclofenac Sodium DRUG

Group A-Intramuscular diclofenac sodium+oral placebo Group B-Oral diclofenac sodium+ intramuscular placebo

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy volunteers
• Adult patients above 18-65 years of age.
• Patients with soft tissue injury/ cut wounds
• Pain score more than or equal to 4 on NRS.
• Patients weight more than or equal to 50kgs.
• If treating physician approves patient participation in the study.
• Not on any medication.

You may not qualify if:

• Received any analgesic within last 12 hours, on the day of visit to ED.
• Patients with fractures
• Allergic to diclofenac.
• Cardio-vascular disease, renal impairment, stroke or any other co-morbidity / chronic illness.
• Pregnancy / Nursing
• Peptic ulcers
• Bleeding disorders
• liver disease
• Bronchial asthma

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

Isma Qureshi

Doha, 3050, Qatar

RECRUITING

Related Publications (6)

• Derry P, Derry S, Moore RA, McQuay HJ. Single dose oral diclofenac for acute postoperative pain in adults. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD004768. doi: 10.1002/14651858.CD004768.pub2.

  PMID: 19370609 BACKGROUND

• Marret E, Kurdi O, Zufferey P, Bonnet F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology. 2005 Jun;102(6):1249-60. doi: 10.1097/00000542-200506000-00027.

  PMID: 15915040 BACKGROUND

• 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.

  PMID: 26993881 BACKGROUND

• Gan TJ, Daniels SE, Singla N, Hamilton DA, Carr DB. A novel injectable formulation of diclofenac compared with intravenous ketorolac or placebo for acute moderate-to-severe pain after abdominal or pelvic surgery: a multicenter, double-blind, randomized, multiple-dose study. Anesth Analg. 2012 Nov;115(5):1212-20. doi: 10.1213/ANE.0b013e3182691bf9. Epub 2012 Aug 10.

  PMID: 22886837 BACKGROUND

• Turturro MA, Paris PM, Seaberg DC. Intramuscular ketorolac versus oral ibuprofen in acute musculoskeletal pain. Ann Emerg Med. 1995 Aug;26(2):117-20. doi: 10.1016/s0196-0644(95)70138-9.

  PMID: 7618770 BACKGROUND

• Ucar R, Biyik M, Ucar E, Polat I, Cifci S, Ataseven H, Demir A. Rectal or intramuscular diclofenac reduces the incidence of pancreatitis afterendoscopic retrograde cholangiopancreatography. Turk J Med Sci. 2016 Jun 23;46(4):1059-63. doi: 10.3906/sag-1502-104.

  PMID: 27513404 BACKGROUND

MeSH Terms

Conditions

Agnosia

Interventions

Diclofenac

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: A computer generated block randomization sequence will be generated and stored with sequential coding known to the clinical pharmacist only. Within the randomization another stratified randomized sequence will be generated, for the patients to be enrolled for the PK study. Among the 300 trial packets prepared for the study, 20 packets will contain one additional code that will indicate the subject to be enrolled in the PK study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Academic Research Associate

Model Details: Double blind randomized trial

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 21, 2018
• Study Start: January 15, 2018
• Primary Completion: April 15, 2018
• Study Completion: April 15, 2018
• Last Updated: March 22, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

QA (1)