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The literature regarding analgesic modalities, their combinations and routes of administrations for patients with pain related to renal colic is expanding. NSAID's (IV ketorolac) and opioids (morphine) constitutes the mainstay of treatment of renal colic either alone or in combinations. Despite their synergism and analgesic superiority when administered together, both classes of these medications possess a set of unfavorable side effects that limit their use. Emerging data of the use of IV lidocaine for patients with renal colic demonstrated good analgesic efficacy and safety profile. However, none of the trials directly compared lidocaine to ketorolac or the combination of both as viable options in patients unable to tolerate or to have serious contraindications to opioids. We designed a double-blinded, randomized, controlled trial to evaluate analgesic efficacy, safety and feasibility of non-opioid analgesics and their combinations in patients with renal colic. The hypothesis and proposed study will try to determine if a combination of IV lidocaine and reduced dose of IV ketorolac is superior to either drug alone and if this non-opioid analgesic modality is effective for controlling pain of renal colic origin.
The investigators designed a double-blind, randomized, clinical trial to evaluate analgesic efficacy, safety and feasibility of non-opioid analgesics IV Lidocaine and IV Ketorolac and combination of both in patients with renal colic. The hypothesis and proposed study will try to determine if a combination of IV lidocaine and IV ketorolac is superior to either drug alone and if this non-opioid analgesic combination is effective for controlling pain of renal colic origin. The trial will compare pain scores at 15 min and 30 min between and within the three treatment groups of the study: IV ketorolac 30mg push and 10 minute normal saline drip placebo, 1.5mg/kg IV lidocaine drip (given over 10 minutes) and normal saline push placebo, or IV ketorolac push and IV lidocaine drip.
Once a patient is enrolled, the on duty ED pharmacist will prepare any one of the three treatment groups based on a predetermined randomization list generated via SPSS 19.0.The study investigators will record pain scores, vital signs, and side effects at baseline, 15, 30 and 60 minutes post-medication administration. If the patient still reports pain of five or greater and requests additional pain relief then morphine at 0.1mg/kg will be given as the rescue analgesic. Blinding of medication from the patient, research team, and staff will be strictly maintained by the pharmacist investigators.
Sample Size Calculation:
Fifty per group or 150 is needed given a standard 1.3 as the minimum clinically significant score and 3.0 as our standard deviation at 80% power and a=.05.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lidocaine and normal saline push | Active Comparator | 1.5mg/kg IV Lidocaine Drip (given over 10 minutes) and normal saline push |
|
| Ketorolac and normal saline drip | Active Comparator | IV Ketorolac Tromethamine 30mg push and 10 minute normal saline drip |
|
| Lidocaine and Ketorolac | Active Comparator | IV Lidocaine Drip and IV Ketorolac Push |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lidocaine | Drug | 1.5 mg/kg IV lidocaine drip (given over 10 minutes) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pain Score at 30 Minutes | The trial will compare the patient's pain score on a 11 point Likert scale, ranging from 0 to 10 with 0 being no pain, 5 moderate pain and 10 very severe pain, at 30 minutes | 30 minutes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sergey Motov, MD | Maimonides Medical Center | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24701420 | Background | Golzari SE, Soleimanpour H, Rahmani F, Zamani Mehr N, Safari S, Heshmat Y, Ebrahimi Bakhtavar H. Therapeutic approaches for renal colic in the emergency department: a review article. Anesth Pain Med. 2014 Feb 13;4(1):e16222. doi: 10.5812/aapm.16222. eCollection 2014 Feb. | |
| Background | Talati, J, Tiselius, H.-G, Albala, D.M, YE, Z. Urolithiasis: Basic Science and Clinical Practice. Springer Science & Business Media, Dec 22, 2012 | ||
| 7827834 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lidocaine and Normal Saline Push | 1.5mg/kg IV Lidocaine Drip (given over 10 minutes) and normal saline push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Normal Saline Push: Normal Saline Push Placebo |
| FG001 | Ketorolac and Normal Saline Drip | IV Ketorolac Tromethamine 30mg push and 10 minute normal saline drip Ketorolac Tromethamine: IV ketorolac 30mg push Normal Saline Drip: Normal Saline Drip Placebo given over 10 minutes |
| FG002 | Lidocaine and Ketorolac | IV Lidocaine Drip and IV Ketorolac Push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Ketorolac Tromethamine: IV ketorolac 30mg push |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lidocaine and Normal Saline Push | 1.5mg/kg IV Lidocaine Drip (given over 10 minutes) and normal saline push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Normal Saline Push: Normal Saline Push Placebo |
| BG001 | Ketorolac and Normal Saline Drip |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Pain Score at 30 Minutes | The trial will compare the patient's pain score on a 11 point Likert scale, ranging from 0 to 10 with 0 being no pain, 5 moderate pain and 10 very severe pain, at 30 minutes | Posted | Mean | Standard Deviation | score on a scale | 30 minutes |
|
2 hours
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lidocaine and Normal Saline Push | 1.5mg/kg IV Lidocaine Drip (given over 10 minutes) and normal saline push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Normal Saline Push: Normal Saline Push Placebo |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Antonios Likourezos | Maimonides Medical Center | 7182836896 | alikourezos@maimonidesmed.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 24, 2018 | Mar 11, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008012 | Lidocaine |
| D020911 | Ketorolac Tromethamine |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 |
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| Ketorolac Tromethamine | Drug | IV ketorolac 30mg push |
|
|
| Normal Saline Drip | Drug | Normal Saline Drip Placebo given over 10 minutes |
|
|
| Normal Saline Push | Drug | Normal Saline Push Placebo |
|
|
| Background |
| Sandhu DP, Iacovou JW, Fletcher MS, Kaisary AV, Philip NH, Arkell DG. A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic. Br J Urol. 1994 Dec;74(6):690-3. doi: 10.1111/j.1464-410x.1994.tb07107.x. |
| 9928687 | Background | Larkin GL, Peacock WF 4th, Pearl SM, Blair GA, D'Amico F. Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic. Am J Emerg Med. 1999 Jan;17(1):6-10. doi: 10.1016/s0735-6757(99)90003-7. |
| 10921813 | Background | O'Connor A, Schug SA, Cardwell H. A comparison of the efficacy and safety of morphine and pethidine as analgesia for suspected renal colic in the emergency setting. J Accid Emerg Med. 2000 Jul;17(4):261-4. doi: 10.1136/emj.17.4.261. |
| 16953530 | Background | Safdar B, Degutis LC, Landry K, Vedere SR, Moscovitz HC, D'Onofrio G. Intravenous morphine plus ketorolac is superior to either drug alone for treatment of acute renal colic. Ann Emerg Med. 2006 Aug;48(2):173-81, 181.e1. doi: 10.1016/j.annemergmed.2006.03.013. |
| 8655940 | Background | Catapano MS. The analgesic efficacy of ketorolac for acute pain. J Emerg Med. 1996 Jan-Feb;14(1):67-75. doi: 10.1016/0736-4679(95)02052-7. |
| 23137151 | Background | Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, Sturkenboom M, Perez-Gutthann S; Safety of Non-Steroidal Anti-Inflammatory Drugs (SOS) Project. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012 Dec 1;35(12):1127-46. doi: 10.2165/11633470-000000000-00000. |
| 2881564 | Background | Duthie DJ, Nimmo WS. Adverse effects of opioid analgesic drugs. Br J Anaesth. 1987 Jan;59(1):61-77. doi: 10.1093/bja/59.1.61. |
| 21714904 | Background | Soleimanpour H, Hassanzadeh K, Mohammadi DA, Vaezi H, Esfanjani RM. Parenteral lidocaine for treatment of intractable renal colic: a case series. J Med Case Rep. 2011 Jun 29;5:256. doi: 10.1186/1752-1947-5-256. |
| 22559856 | Background | Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol. 2012 May 4;12:13. doi: 10.1186/1471-2490-12-13. |
| 30770244 | Derived | Motov S, Fassassi C, Drapkin J, Butt M, Hossain R, Likourezos A, Monfort R, Brady J, Rothberger N, Mann SS, Flom P, Gulati V, Marshall J. Comparison of intravenous lidocaine/ketorolac combination to either analgesic alone for suspected renal colic pain in the ED. Am J Emerg Med. 2020 Feb;38(2):165-172. doi: 10.1016/j.ajem.2019.01.048. Epub 2019 Jan 30. |
IV Ketorolac Tromethamine 30mg push and 10 minute normal saline drip Ketorolac Tromethamine: IV ketorolac 30mg push Normal Saline Drip: Normal Saline Drip Placebo given over 10 minutes |
| BG002 | Lidocaine and Ketorolac | IV Lidocaine Drip and IV Ketorolac Push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Ketorolac Tromethamine: IV ketorolac 30mg push |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Lidocaine and Ketorolac | IV Lidocaine Drip and IV Ketorolac Push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Ketorolac Tromethamine: IV ketorolac 30mg push |
|
|
| 0 |
| 50 |
| 0 |
| 50 |
| 0 |
| 50 |
| EG001 | Ketorolac and Normal Saline Drip | IV Ketorolac Tromethamine 30mg push and 10 minute normal saline drip Ketorolac Tromethamine: IV ketorolac 30mg push Normal Saline Drip: Normal Saline Drip Placebo given over 10 minutes | 0 | 50 | 0 | 50 | 0 | 50 |
| EG002 | Lidocaine and Ketorolac | IV Lidocaine Drip and IV Ketorolac Push Lidocaine: 1.5 mg/kg IV lidocaine drip (given over 10 minutes) Ketorolac Tromethamine: IV ketorolac 30mg push | 0 | 50 | 0 | 50 | 0 | 50 |
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| Aniline Compounds |
| D000588 | Amines |
| D007213 | Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Male |
|