Ketorolac Effects on Post-operative Pain and Bone Healing

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01133639
• Collaborator: American College of Foot and Ankle Surgeons (Other)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 21.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This will be a randomized double-blind placebo-controlled clinical trial that will accept all eligible consecutive patients undergoing elective Kalish bunionectomies. Patients will be randomized into either receiving ketorolac (30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days) plus standard of care or placebo plus standard of care. The purpose of this study is to evaluate the effects of ketorolac plus standard of care on post-operative pain control and radiographic osseous healing. Patients will be assessed for pain via a validated pain questionnaire and for delayed unions via a radiographic scoring system shown to have both high inter- and intra-observer reliability by a blinded board certified radiologist. Additional outcomes of bunionectomy procedures will also be evaluated including adverse events and time to regular shoe gear and activities.

Condition or Disease	Intervention/Treatment	Phase
Bunion	Drug: Ketorolac; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Does Ketorolac Delay Bone Healing and Improve Post-operative Pain?: A Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo plus standard of care	Drug: Placebo; Placebo plus standard of care
Experimental: Ketorolac 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care	Drug: Ketorolac; 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care

Outcome Measures

Primary Outcome Measures

1. Post-Operative Pain [Post-Operative Day 2]

   18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

2. Osseous Healing [3 months]

   Radiographic assessment by a blinded board certified radiologist

Secondary Outcome Measures

1. Post-operative Activity Recovery [up to 3 months]

   Functional Recovery Index

2. Adverse Events [1 week]

   Comparison of adverse events between the two study arms

3. Quantity of Narcotic Medication [1 week]

   Comparison of quantity of narcotic medication utilized within the two study arms

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Hallux abductus with bunion deformity

• Adult patients as defined by >=18 years old and <= 65 years old

• Subject has adequate perfusion, verified by the surgeon, which is defined by palpable pedal pulses

• Subject has voluntarily signed and dated an informed consent form, approved by IRB, and provided HIPAA (or other applicable privacy regulation) authorization prior to any participation in the study

• Subject agrees not to take any new medications, dietary supplements, or alternative therapies during the study period (approximately 12 weeks)

• Subject is interested in participating in the study and willing to comply with the study protocol

• Patient has pain related to a bunion deformity but pain-free metatarsalphalangeal joint (MTPJ) range of motion that is not functionally adapted

• Adequate bone density to withstand a Kalish bunionectomy procedure

• No frontal plane hallux deformity

• Minimal abnormality of the PASA

• Normal to minimally malaligned sagittal plane position of the first metatarsal

• Failure of conservative treatment

• General Pre-operative Radiographic Angle Criteria† - 10-15 degree IMA in rectus feet*

• 20-25 degree TAA in adducted feet* - 15-20 degree IMA in rectus feet if wide metatarsal head width - 25-30 degree TAA in adducted feet if wide metatarsal head width IMA=intermetatarsal angle; TAA=total adductus angle *If the pre-operative IMA is <15 degree, only the IMA will be used pre-operatively. For IMA >=15, the total adductus angle will be used †These are general guidelines and the width of the metatarsal as well as the presence of positional, structural, or combined first ray deformity may also influence procedure selection.

Exclusion Criteria:

• a history of an allergic-type reaction in response to exposure to aspirin, phenylacetic acid derivatives, or other NSAIDs

• hypersensitivity to ketorolac tromethamine, or to any product component

• any known bleeding risk or bleeding disorder, suspected or confirmed

• history of or active cerebrovascular bleeding, suspected or confirmed

• concomitant aspirin or NSAID use where the patient may not be advised to discontinue the medication during the study

• concomitant pentoxifylline use

• concomitant probenecid use

• coronary artery bypass graft (CABG) surgery within one year of the procedure

• any history of gastrointestinal bleeding/perforation, gastrointestinal ulcer, severe peptic ulcer disease, or severe inflammatory bowel disease

• hemorrhagic diathesis, suspected or confirmed

• incomplete intraoperative hemostasis

• pre-operative serum creatinine > 1.5 ml/dL or blood urea nitrogen level > 22 mg/dL

• any history of renal impairment or risk of renal failure due to volume depletion

• Patients with a known allergy, contraindication and/or intolerance for oxycodone 5mg - acetaminophen 325 mg will be excluded from the study.

• Patients with a known allergy, contraindication, and/or intolerance for the local anesthetic (bupivicaine) or any of the standardized intra-operative opioids and anti-emetics administered by the anesthesiologist

• Patients with a history of fibromyalgia or opioid abuse

• History of chronic regional pain syndrome or diagnosis of any chronic pain syndrome, patients requiring routine methadone or other opioids

• Neuropathy or radiculopathy

• Subject has alcohol or substance abuse, dementia, brain metastases, or other cognitive disorders that may interfere with pain assessment and the post-operative course outlined by the surgeon

• American Society of Anesthesiologists (ASA) Physical Status class four or higher

• women who are pregnant, planning on becoming pregnant, or breast feeding

• presence of active local or systemic infection

• subject has a myocardial infarction in the last twelve months

• Patients who are not candidates for a Kalish bunionectomy due to the preoperative deformity as well as other study exclusions are:

• Absent pedal pulses or ABI < 0.9 and > 1.2

• Concomitant midfoot and rearfoot procedures

• Moderate to high abnormal PASA angles

• Significant sagittal plane first metatarsal deformity

• Moderate to severe osteoporosis as evaluated by preoperative radiographs and/or bone mineral density tests

• Revision cases

• History of previous infections, radiation treatment, or current infection related to the surgical site

• History of previous trauma of the first metatarsal or first ray

• Subject has known immunosuppression (HIV, recent chemotherapy, organ transplant)

• Patients taking systemic steroid (patients taking less than 5 mg of prednisone, inhaled steroids for asthma or chronic obstructive pulmonary disease, topical or optical steroids will not be excluded)

• Subject has active malignancy, excluding cutaneous malignancies except melanoma Pregnancy Elective bunion surgery will not be performed if the patient is pregnant or planning on becoming pregnant during this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• American College of Foot and Ankle Surgeons

Investigators

• Principal Investigator: Emily A Cook, DPM, MPH, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 13, 2010

More Information

Publications

None provided.

• Responsible Party: Emily Cook, Instructor in Surgery, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01133639
• Other Study ID Numbers: 2010P000047
• First Posted: May 31, 2010
• Last Update Posted: Aug 21, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Pain, Postoperative; Ketorolac

Study Results

Participant Flow

Recruitment Details	18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Ketorolac	Total
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Race and Ethnicity Not Collected () []
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Post-Operative Pain
Description	18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.
Time Frame	Post-Operative Day 2

Outcome Measure Data

Analysis Population Description

18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Measure Participants	0	0

2. Primary Outcome

Title	Osseous Healing
Description	Radiographic assessment by a blinded board certified radiologist
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Measure Participants	0	0

3. Secondary Outcome

Title	Post-operative Activity Recovery
Description	Functional Recovery Index
Time Frame	up to 3 months

Outcome Measure Data

Analysis Population Description

18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Measure Participants	0	0

4. Secondary Outcome

Title	Adverse Events
Description	Comparison of adverse events between the two study arms
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Measure Participants	0	0

5. Secondary Outcome

Title	Quantity of Narcotic Medication
Description	Comparison of quantity of narcotic medication utilized within the two study arms
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

18 subjects were enrolled & completed the study. Pharmacy held the randomization table. PI left institution & was never unblinded (because there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. Study was terminated due to lack of administrative support 2/2012 & all data has been destroyed.

Arm/Group Title	Placebo	Ketorolac
Arm/Group Description	Placebo plus standard of care Placebo: Placebo plus standard of care	30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
Measure Participants	0	0

Adverse Events

Time Frame	18 subjects were enrolled & all subjects completed the study. Adverse events were monitored & assessed through study completion for each subject. Pharmacy held the randomization table. Per study protocol, any adverse event would have required unblinding of the PI & reporting to the IRB. PI left institution & was never unblinded (b/c there were never any AEs). Therefore, do not know which subjects were in the placebo vs ketorolac arms. But no adverse events occurred with any of the subjects.
Adverse Event Reporting Description	Pharmacy maintained the randomization table. The PI was blinded as she was also one of the surgeons in the study. The PI left the institution & was never unblinded or given the randomization table because there were never any adverse events & the data was never analyzed. PI terminated the study due to lack of administrative support. Study terminated 2/2012 & data has been destroyed and was never analyzed. Do not know which subjects were in placebo vs ketorolac arm.
Arm/Group Title	Placebo or Ketorolac
Arm/Group Description	Placebo: Placebo plus standard of care or Ketorolac 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care Ketorolac: 30 mg IV dose intra-operatively followed by 10 mg orally every 8 hours for five days plus standard of care
All Cause Mortality
	Placebo or Ketorolac
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Serious Adverse Events
	Placebo or Ketorolac
	Affected / at Risk (%)	# Events
Total	0/18 (0%)
Other (Not Including Serious) Adverse Events
	Placebo or Ketorolac
	Affected / at Risk (%)	# Events
Total	0/18 (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.