Efficacy Study of Different Analgesic Options in Kidney Stone Pain Management

Sponsor

Hamad Medical Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT02187614

Collaborator

(none)

1,645

Enrollment

Location

Arms

Duration (Months)

236.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Abdominal pain is one of the most common presentations to an emergency department (ED). Among patients presenting with abdominal pain, a common diagnosis in the Middle East is renal colic (urolithiasis or Kidney stones). As the patients with renal colic writhe around in agonizing pain, the first priority in an ED from a patient's perspective is fast and safe analgesia and to be pain free as early as possible. There are variations in physician preference to choose initial analgesic drug for managing such pain. Commonly used drugs are:

Opioids such as Morphine or Fentanyl
Non steroidal drugs such as Diclofenac, Ketorolac or Brufen
and Paracetamol intravenous injection.

A robust evidence in comparison of diclofenac versus morphine and paracetamol is lacking. This study is design to obtain data on efficacy of these three drugs within 30 minutes in a non inferiority trail.

Condition or Disease	Intervention/Treatment	Phase
Renal Colic Urinary Calculi	Drug: Diclofenac Drug: Morphine Drug: Paracetamol Drug: Placebos	Phase 4

Detailed Description

This will be a double blind RCT, where participants will be enrolled consecutively after meeting eligibility criteria and obtaining a written informed consent. They will be assign to one of the three study arms by computer generated randomization process. The study packets will be prepared by a dedicated nurse or pharmacist who will not a part of investigating team. Each Patients will receive one analgesic drug (active drug) and two placebos. Drugs will be given as one intramuscular injection and two intravenous solutions.

Pain score will be recorded using NRS at 0, 30, 60, and 90 minutes. Data will be collected on standard Data collection form. Each participant will receive analgesia from study packet which contains, one active drug and two placebos to be administer as one intramuscular and two intravenous solutions. At any given time every patient will receive one analgesia from either Diclofenac, Paracetamol or Morphine. If patient pain does not respond to initial treatments, at 30 minutes a rescue analgesia in form of morphine will be administered till patient is pain free or NRS<=2 or adverse event to morphine.

Based on the results of previous studies (1-3), proportion of patients achieving more than 50% pain reduction, is between 65-75% for diclofenac, morphine and paracetamol when compared with other drugs. In each group, 437 patients are required to detect a difference of 10% in primary outcome, in a superiority trial with power (1-beta) of 90% and significance level (alpha) of 5% in this study. Considering 15% extra, total sample size required in this superiority trial will be 1507 patients in total.

Data will be collected on a standard data recording form and it will be converted to electronic excel sheet hiding patient identifiable details. Continuous variables will be presented as mean with standard deviation (SD). Categorical variables will be calculated as proportions and presented with 95% Confidence interval (CI). Statistical analyses will be undertaken using Stata 12.0 (College Station, Texas).

Study Design

Study Type:

Interventional

Actual Enrollment :

1645 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double Blind, Multi-arm Randomized Control Trial, for Efficacy of Intramuscular Diclofenac Versus Intravenous Morphine Versus Intravenous Paracetamol, in Renal Colic Emergency Department Pain Management

Study Start Date :

Aug 1, 2014

Actual Primary Completion Date :

Feb 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diclofenac and Placebos Participants in this group will receive a Diclofenac 75 mg intramuscular injection, and two placebo saline solutions intravenously.	Drug: Diclofenac Other Names: Voltaren Diclofen Diclorex Drug: Placebos Other Names: saline solution
Active Comparator: Morphine and Placebos Participants in this group will receive Morphine 0.1 mg/kg intravenously, along with an additional intravenous placebo and an intramuscular placebo injection.	Drug: Morphine Other Names: Morphine sulphate Drug: Placebos Other Names: saline solution
Active Comparator: Paracetamol and Placebos participants in this group will receive intravenous Paracetamol 1 gm solution, along with an additional intravenous placebo and an intramuscular placebo injection.	Drug: Paracetamol Other Names: Perfalgan Acetaminophen Drug: Placebos Other Names: saline solution

Arm

Intervention/Treatment

Experimental: Diclofenac and Placebos

Participants in this group will receive a Diclofenac 75 mg intramuscular injection, and two placebo saline solutions intravenously.

Drug: Diclofenac

Other Names:

Voltaren

Diclofen

Diclorex

Drug: Placebos

Other Names:

saline solution

Active Comparator: Morphine and Placebos

Participants in this group will receive Morphine 0.1 mg/kg intravenously, along with an additional intravenous placebo and an intramuscular placebo injection.

Drug: Morphine

Other Names:

Morphine sulphate

Drug: Placebos

Other Names:

saline solution

Active Comparator: Paracetamol and Placebos

participants in this group will receive intravenous Paracetamol 1 gm solution, along with an additional intravenous placebo and an intramuscular placebo injection.

Drug: Paracetamol

Other Names:

Perfalgan

Acetaminophen

Drug: Placebos

Other Names:

saline solution

Outcome Measures

Primary Outcome Measures

The proportion of patients achieving a reduction of >50% on Numerical Rating Scale (NRS-11) from the initial NRS recorded at the end of 30 minutes in each study arm. [at 30 minutes after analgesia]

Secondary Outcome Measures

reduction in mean NRS [at 30, 60 and 90 minutes after analgesia]

Other Outcome Measures

adverse event rate [Within 14 days of ED visit]
total analgesia requirement to get pain score (NRS) less than or equal to 2. [by 90 minutes]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age >=18 years and < 65 years
Acute onset, one side flank or loin pain, with or without radiation to groin or genital areas.
Pain intensity on NRS more than or equal to 4. (Moderate to Severe Pain)
Diagnosis confirmed by non contrast CT KUB within the ED visit.

Exclusion Criteria:

Traumatic flank pain
Pregnancy
Known renal failure or impairment
Known allergy to morphine, diclofenac or paracetamol
Bronchial asthma
Previously enrolled in the study.
Use of any analgesia in last 6 hour.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emergency Department, Hamad General Hospital.	Doha		Qatar	3050

Sponsors and Collaborators

Hamad Medical Corporation

Investigators

Principal Investigator: Dr.Sameer A. Pathan, MBBS, MCEM, Hamad Medical Corporation
Principal Investigator: Prof. Peter A Cameron, MD,FACEM, Hamad Medical Corporation