The Use of Intranasal Ketoralac for Pain Management (Sprix)

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01736358
• Collaborator: (none)
• Enrollment: 50
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Despite an overall reduction in the perioperative complication rate, post operative pain management after ureteroscopic removal of stones (URS) remains a major factor delaying discharge of patients. The investigators hypothesize that perioperative usage of intranasal ketorolac will provide a reduction in post operative opioid requirements, better post operative pain control, higher anesthesia satisfaction and faster recovery.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain Management; Urolithiasis	Drug: Intranasal Ketoralac; Drug: Placebo	Phase 4

Detailed Description

The prevalence and incidence of urolithiasis, or kidney stone disease, are increasing in the general population. Life-time incidence of urolithiasis is estimated to be between 5%- 12%. The treatment of kidney stones depends on stone type and size, symptom severity, and the presence of obstruction.

URS is a common ambulatory procedure as improved technological advances and increased clinical utilization have helped decrease postoperative complications. Despite an overall reduction in the perioperative complication rate, post operative pain management after URS remains a major factor delaying discharge of patients.

Post operative pain after URS is usually treated with opioids and non steroidal anti inflammatory drugs. Intranasal ketorolac (SprixTM) is an FDA approved pain formulation for short term management (5 days) of moderate to moderately severe pain that requires analgesia at the opioid level. The efficacy of intranasal ketorolac formulation was demonstrated in placebo-controlled studies in patients following major surgeries.

The primary objective of the study is to evaluate the role perioperative usage of single-dose of intranasal ketorolac on immediate post operative opioid requirements. Secondary objectives of the study are to (a) evaluate the post operative pain score 30 minutes after surgery, 1 hour after surgery, and 2 hours after surgery, (b) find the incidence of immediate (until discharge) and 24hrs post operative side effects in the target population, (c) find the level of anesthesia satisfaction in the target population, (d) find the time to discharge in the target population, (e) compare the two groups post anesthesia discharge score.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Evaluating Post-operative Pain Management Efficacy of Intra Nasal Ketorolac in Ambulatory Urological Surgeries-A Randomized Double-blinded Placebo Controlled Study
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal Ketoralac A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril.	Drug: Intranasal Ketoralac; 15.75 mg of Sprix in each nostril 20 minutes before end of surgery; Other Names: Sprix
Placebo Comparator: Placebo A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril.	Drug: Placebo; 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery

Outcome Measures

Primary Outcome Measures

1. Post-operative Opioid Requirements [3 hours after surgery]

   this study will assess the effect of perioperative usage of single-dose of intranasal ketorolac on post operative opioid requirements within 3 hours after surgery.

Secondary Outcome Measures

1. Post Operative Pain Score [30 minutes after surgery]

   To evaluate the post operative pain score using the Visual Analog Scale (VAS) 30 minutes after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.

2. Post Operative Pain Score [1 hour after surgery]

   To evaluate the post operative pain score using the Visual Analog Scale (VAS) 1 hour after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.

3. Post Operative Pain Scale [2 hours after surgery]

   To evaluate the post operative pain score using the Visual Analog Scale (VAS) 2 hours after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.

Other Outcome Measures

1. Incidence of Postoperative Side Effects [24 hours after procedure]

   To find the incidence of immediate (until discharge) and 24hrs post operative side effects in the target population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ureteroscopic stone removal surgeries with stenting

• Age ≥ 18 years and < 65 years

• Stable patient with stable vital signs

• Mentally competent and is able to understand consent form

Exclusion Criteria:

• Unstable patients

• Patients with multiple trauma sites

• Patients with allergies to ketorolac or any of the components in the nasal spray preparation

• Patients with active peptic ulcer disease

• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

• Renal disease or at risk for renal failure due to volume depletion

• Pregnant or nursing mothers

• Nasal abnormality or illness that could affect the absorption of intranasal medication (such as: nasal discharge, rhinitis, acute upper respiratory infection, acute epistaxis, nasal polyp, nasal tumor)

• Any other contraindication to the use of Sprix, or in whom use of Sprix would not be consistent with the approved package insert

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center- Weiler Division	Bronx	New York	United States	10461

Sponsors and Collaborators

• Montefiore Medical Center

Investigators

• Study Director: Singh Nair, MD, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ahn ST, Kim JH, Park JY, Moon du G, Bae JH. Acute postoperative pain after ureteroscopic removal of stone: incidence and risk factors. Korean J Urol. 2012 Jan;53(1):34-9. doi: 10.4111/kju.2012.53.1.34. Epub 2012 Jan 25.
• Bromwich EJ, Lockyer R, Keoghane SR. Day-case rigid and flexible ureteroscopy. Ann R Coll Surg Engl. 2007 Jul;89(5):526-8.
• Brown C, Moodie J, Bisley E, Bynum L. Intranasal ketorolac for postoperative pain: a phase 3, double-blind, randomized study. Pain Med. 2009 Sep;10(6):1106-14. doi: 10.1111/j.1526-4637.2009.00647.x. Epub 2009 Jul 6. Erratum in: Pain Med. 2011 Jun;12(6):990. Dosage error in published abstract; MEDLINE/PubMed abstract corrected.
• Cheung MC, Lee F, Leung YL, Wong BB, Chu SM, Tam PC. Outpatient ureteroscopy: predictive factors for postoperative events. Urology. 2001 Dec;58(6):914-8.
• Erhard M, Salwen J, Bagley DH. Ureteroscopic removal of mid and proximal ureteral calculi. J Urol. 1996 Jan;155(1):38-42. Erratum in: J Urol 1996 Mar;155(3):1039.
• Grant GM, Mehlisch DR. Intranasal ketorolac for pain secondary to third molar impaction surgery: a randomized, double-blind, placebo-controlled trial. J Oral Maxillofac Surg. 2010 May;68(5):1025-31. doi: 10.1016/j.joms.2009.10.023. Epub 2010 Mar 5.
• McAleer SD, Majid O, Venables E, Polack T, Sheikh MS. Pharmacokinetics and safety of ketorolac following single intranasal and intramuscular administration in healthy volunteers. J Clin Pharmacol. 2007 Jan;47(1):13-8.
• Moodie JE, Brown CR, Bisley EJ, Weber HU, Bynum L. The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Anesth Analg. 2008 Dec;107(6):2025-31. doi: 10.1213/ane.0b013e318188b736. Erratum in: Anesth Analg. 2009 Mar;108(3):991. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text.
• Pak CY, Resnick MI, Preminger GM. Ethnic and geographic diversity of stone disease. Urology. 1997 Oct;50(4):504-7.
• Peschel R, Janetschek G, Bartsch G. Extracorporeal shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective randomized study. J Urol. 1999 Dec;162(6):1909-12.
• Saigal CS, Joyce G, Timilsina AR; Urologic Diseases in America Project. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005 Oct;68(4):1808-14.
• Singla N, Singla S, Minkowitz HS, Moodie J, Brown C. Intranasal ketorolac for acute postoperative pain. Curr Med Res Opin. 2010 Aug;26(8):1915-23. doi: 10.1185/03007995.2010.495564. Erratum in: Curr Med Res Opin. 2012 Jun;28(6):1052.
• Tiselius HG. Epidemiology and medical management of stone disease. BJU Int. 2003 May;91(8):758-67. Review.

• Responsible Party: Singh Nair, Associate Professor, Dept of Urology, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT01736358
• Other Study ID Numbers: 12-02-244
• First Posted: Nov 29, 2012
• Last Update Posted: Feb 13, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Singh Nair, Associate Professor, Dept of Urology, Montefiore Medical Center: Sprix; Intranasal ketoralac; Ketoralac; Urolithiasis; Kidney stone; Uretal stone; Ureteroscopic removal of stones; URS; Pain management; Pain
• Additional relevant MeSH terms: Urolithiasis; Urinary Calculi; Ketorolac

Study Results

Participant Flow

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Period Title: Overall Study
STARTED	25	25
COMPLETED	20	23
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Intranasal Ketoralac	Placebo	Total
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery	Total of all reporting groups
Overall Participants	20	23	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	23 100%	43 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	47 (12.4)	49 (9.3)	48 (11)
Sex: Female, Male (Count of Participants)
Female	10 50%	11 47.8%	21 48.8%
Male	10 50%	12 52.2%	22 51.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	23 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Post-operative Opioid Requirements
Description	this study will assess the effect of perioperative usage of single-dose of intranasal ketorolac on post operative opioid requirements within 3 hours after surgery.
Time Frame	3 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Measure Participants	20	23
Median (Inter-Quartile Range) [mg]	27.43	30

2. Secondary Outcome

Title	Post Operative Pain Score
Description	To evaluate the post operative pain score using the Visual Analog Scale (VAS) 30 minutes after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.
Time Frame	30 minutes after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Measure Participants	20	23
Median (Inter-Quartile Range) [score on a scale]	4	3.5

3. Secondary Outcome

Title	Post Operative Pain Score
Description	To evaluate the post operative pain score using the Visual Analog Scale (VAS) 1 hour after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.
Time Frame	1 hour after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Measure Participants	20	23
Median (Inter-Quartile Range) [score on a scale]	3.5	4.5

4. Secondary Outcome

Title	Post Operative Pain Scale
Description	To evaluate the post operative pain score using the Visual Analog Scale (VAS) 2 hours after surgery. The scale for VAS is 0 is no pain to 10 being the worst pain.
Time Frame	2 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Measure Participants	20	23
Median (Inter-Quartile Range) [score on a scale]	4	3

5. Other Pre-specified Outcome

Title	Incidence of Postoperative Side Effects
Description	To find the incidence of immediate (until discharge) and 24hrs post operative side effects in the target population.
Time Frame	24 hours after procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intranasal Ketoralac	Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery	A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
Measure Participants	20	23
Number [number of events]	0	0

Adverse Events

Arm/Group Title	Intranasal Ketoralac		Placebo
Arm/Group Description	A single dose of Sprix (31.5 mg) will be administered to patients 20 minutes before the end of surgery. 15.75 mg of Sprix will be sprayed in each nostril. Intranasal Ketoralac: 15.75 mg of Sprix in each nostril 20 minutes before end of surgery		A single dose of placebo will be administered 20 minutes before the end of surgery. 15.75 mg of the placebo will be sprayed in each nostril. Placebo: 15.75 mg of placebo will be administered in each nostril 20 minutes before the end of surgery
All Cause Mortality
	Intranasal Ketoralac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)
Serious Adverse Events
	Intranasal Ketoralac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Intranasal Ketoralac		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/23 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.