Anesthesia for Pain After Ankle Fracture Surgery

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT02950558
• Collaborator: (none)
• Enrollment: 14
• Locations: 2
• Arms: 2
• Actual Duration (Months): 24.7
• Patients Per Site: 7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This pilot study will test the hypothesis that prolonged regional peripheral nerve block will reduce development of chronic pain in patients undergoing surgery for ankle fracture compared to standard of care. Subjects will be followed for one year.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain; Ankle Fracture Surgery; Regional Anesthesia	Drug: Ropivacaine; Procedure: Nerve block	Phase 4

Detailed Description

This pilot study will test the hypothesis that prolonged regional peripheral nerve block will reduce development of chronic pain in patients undergoing surgery for ankle fracture. Regional nerve block using local anesthetics delivered by ambulatory pump is used in some types of surgeries but is not routine for ankle fracture patients in our hospitals. Patients will be randomized to standard care (single shot peripheral nerve block prior to surgery) or experimental (the same single shot nerve block, followed by continuous popliteal nerve block with ropivacaine starting just after surgery). The primary outcome will be scores on a validated ankle/foot pain questionnaire that includes questions on function. Subjects will be followed for one year. Secondary outcome will be postoperative opioid use.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study: Extended Regional Anesthesia to Prevent Chronic Pain After Ankle Fracture Surgery
• Actual Study Start Date: May 29, 2018
• Actual Primary Completion Date: Nov 14, 2019
• Actual Study Completion Date: Jun 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ropivacaine Single injection of ropivacaine immediately prior to surgery	Drug: Ropivacaine; Single injection of ropivacaine immediately prior to surgery.; Other Names: Naropin
Experimental: Ropivacaine plus Nerve Block Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block.	Drug: Ropivacaine; Single injection of ropivacaine immediately prior to surgery.; Other Names: Naropin ; Procedure: Nerve block; insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.; Other Names: no other name

Outcome Measures

Primary Outcome Measures

1. Pain Score at 12 Months - Experimental Group vs. Control Group [at 12 months post surgery]

   Patients will complete Self-Administered Foot and Ankle Questionnaire (SEFAS) at 12 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.

Secondary Outcome Measures

1. Pain Score at 2 Weeks - Experimental Group vs. Control Group [at 2 weeks post surgery]

   Patients will complete Self-Administered Foot and Ankle Questionnaire at 2 weeks post surgery. For this instrument, 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome

2. Pain Score at 3 Months - Experimental Group vs. Control Group [at 3 months post surgery]

   Patients will complete Self-Administered Foot and Ankle Questionnaire at 3 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.

3. Pain Score at 6 Months - Experimental Group vs. Control Group [at 6 months post surgery]

   Patients will complete Self-Administered Foot and Ankle Questionnaire at 6 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.

4. Incidence of Chronic Ankle Pain Diagnoses - Experimental Group vs. Control Group [at 1 year post surgery]

   Incidence of chronic ankle pain diagnoses one year after surgery obtained from the medical record was originally planned but proved difficult to obtain. Here we provide the number of patients with a 12 month Self-Administered Foot and Ankle Questionnaire score lower than 40 at the 12 month time point. For this instrument, 48 = no pain or disability; 0 = maximum pain and disability. Scores of 40 below were interpreted to indicate ongoing ankle pain of significance for pain and function, for example, at least 8 of the 12 questions being scored less than the optimal value of 4. Scores from 40 to 48 were interpreted as indicating normal or near normal function of the affected ankle.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Referred for surgery for open reduction and internal fixation for ankle fracture

Exclusion Criteria:

• Unable to give informed consent in English

• Unable to complete surveys in English

• Unable to understand instructions for using pump in English

• Unavailable for followup

• Polytrauma; undergoing other surgeries or having other orthopedic injuries related to the precipitating cause of the ankle fracture

• Infection

• Peripheral vascular disease

• Diabetes

• Currently undergoing chemotherapy

• Pregnancy

• Currently lactating

• Heart disease or heart rhythm disorder or taking anti-arrhythmic drugs

• Severe renal impairment (Class 3 or worse kidney disease)

• Liver disease (cirrhosis or liver failure)

• Prior allergic reaction to any type of local anesthetic

• Taking therapeutic doses of anti-coagulants or anti-platelet therapy (prophylactic doses started because of hospital admission are not an exclusion)

• Currently taking antidepressants or other psychiatric medications

• Single shot local nerve block prior to surgery was ineffective

• Selected for neuraxial anesthesia rather than general anesthesia for the open reduction surgery

• Already receiving chronic analgesic therapy for a separate chronic pain condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45216
2	UC Health West Chester Hosptial	West Chester	Ohio	United States	45069

Sponsors and Collaborators

• University of Cincinnati

Investigators

• Principal Investigator: Jun-Ming Zhang, MD, MSc, University of Cincinnati

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2018
• Statistical Analysis Plan - Dec 14, 2017

More Information

Publications

None provided.

• Responsible Party: Jun-ming Zhang, Professor of Anesthesia, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT02950558
• Other Study ID Numbers: Zhang2016
• First Posted: Nov 1, 2016
• Last Update Posted: Jul 2, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Chronic Pain; Fractures, Bone; Ankle Fractures; Ropivacaine

Study Results

Participant Flow

Recruitment Details	Patients scheduled for open reduction and fixation of an ankle fracture were recruited from hospitals and outpatient surgery centers associated with the University of Cincinnati. Recruitment was delayed by a national ropivacaine shortage. Recruitment occurred between May 2018 and June 2019.

Arm/Group Title	Standard Care	Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Period Title: Overall Study
STARTED	8	6
12 Month Pain Questionnaire	6	6
COMPLETED	6	6
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Standard Care	Ropivacaine Pump	Total
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.	Total of all reporting groups
Overall Participants	8	6	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	6 100%	14 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.13 (10.09)	43.17 (15.41)	43.71 (12.10)
Sex: Female, Male (Count of Participants)
Female	2 25%	5 83.3%	7 50%
Male	6 75%	1 16.7%	7 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 12.5%	1 16.7%	2 14.3%
White	7 87.5%	5 83.3%	12 85.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	6 100%	14 100%
BMI (body mass index) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.17 (5.538)	31.53 (3.886)	31.32 (4.728)

Outcome Measures

1. Primary Outcome

Title	Pain Score at 12 Months - Experimental Group vs. Control Group
Description	Patients will complete Self-Administered Foot and Ankle Questionnaire (SEFAS) at 12 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.
Time Frame	at 12 months post surgery

Outcome Measure Data

Analysis Population Description

2 subjects in standard care group were lost to follow-up and did not complete 12 month questionnaire but their questionnaires from earlier time points were included in the analyses.

Arm/Group Title	Standard Care	Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Measure Participants	6	6
Mean (Standard Deviation) [units on a scale]	36.33 (9.543)	44.00 (1.414)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Care, Ropivacaine Pump
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1269
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Pain Score at 2 Weeks - Experimental Group vs. Control Group
Description	Patients will complete Self-Administered Foot and Ankle Questionnaire at 2 weeks post surgery. For this instrument, 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome
Time Frame	at 2 weeks post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Care	Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Measure Participants	8	6
Mean (Standard Deviation) [units on a scale]	16.22 (6.637)	13.67 (2.082)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Care, Ropivacaine Pump
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8808
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Pain Score at 3 Months - Experimental Group vs. Control Group
Description	Patients will complete Self-Administered Foot and Ankle Questionnaire at 3 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.
Time Frame	at 3 months post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Care	Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Measure Participants	8	6
Mean (Standard Deviation) [units on a scale]	26.25 (7.869)	35.71 (5.489)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Care, Ropivacaine Pump
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0382
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Pain Score at 6 Months - Experimental Group vs. Control Group
Description	Patients will complete Self-Administered Foot and Ankle Questionnaire at 6 months post surgery. 0 = worst possible pain and function, 48 = no pain or dysfunction. Higher scores indicate a better outcome.
Time Frame	at 6 months post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Care	Ropivacaine Ppump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Measure Participants	6	6
Mean (Standard Deviation) [units on a scale]	34.00 (9.011)	37.67 (3.724)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Care, Ropivacaine Pump
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4696
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Incidence of Chronic Ankle Pain Diagnoses - Experimental Group vs. Control Group
Description	Incidence of chronic ankle pain diagnoses one year after surgery obtained from the medical record was originally planned but proved difficult to obtain. Here we provide the number of patients with a 12 month Self-Administered Foot and Ankle Questionnaire score lower than 40 at the 12 month time point. For this instrument, 48 = no pain or disability; 0 = maximum pain and disability. Scores of 40 below were interpreted to indicate ongoing ankle pain of significance for pain and function, for example, at least 8 of the 12 questions being scored less than the optimal value of 4. Scores from 40 to 48 were interpreted as indicating normal or near normal function of the affected ankle.
Time Frame	at 1 year post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Care	Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.	Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
Measure Participants	6	6
SEFAS Score >=40	3 37.5%	6 100%
SEFAS Score <40	3 37.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Care, Ropivacaine Pump
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1818
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Subjects were contacted daily by phone for the first five days after surgery (which corresponded to the duration of ambulatory ropivacaine pump use for subjects in the experimental group). Medical chart records were reviewed for adverse events for 3 months following the surgery.
Adverse Event Reporting Description	The protocol incorporated FDA adverse event definitions and Good Clinical Practices.
Arm/Group Title	Standard Care		Ropivacaine Pump
Arm/Group Description	Single injection of ropivacaine immediately prior to surgery Ropivacaine: Single injection of ropivacaine immediately prior to surgery.		Single injection of ropivacaine immediately prior to surgery plus 5 day ambulatory popliteal nerve block. Ropivacaine: Single injection of ropivacaine immediately prior to surgery. Nerve block: insertion of catheter to deliver continuous 5 day popliteal sciatic nerve block using a disposable ambulatory pain pump.
All Cause Mortality
	Standard Care		Ropivacaine Pump
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)
Serious Adverse Events
	Standard Care		Ropivacaine Pump
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Standard Care		Ropivacaine Pump
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		3/6 (50%)
Gastrointestinal disorders
Colitis	0/8 (0%)	0	1/6 (16.7%)	1
General disorders
Lightheadedness, nausea,headache	0/8 (0%)	0	1/6 (16.7%)	1
Injury, poisoning and procedural complications
metalic taste around lips	0/8 (0%)	0	1/6 (16.7%)	1
Surgical and medical procedures
wound dehiscence	1/8 (12.5%)	1	0/6 (0%)	0

Limitations/Caveats

A problem encountered was that only 1 of the 6 subjects in the pump group received the full 5 days of treatment. The others discontinued using the pump early, primarily due to problems with catheter dislodgement/leakage. As specified in the statistical analysis plan, these subjects were all analyzed with intent-to-treat protocol and are included in the pump group data presented. Also, by chance, the distribution of males and females between the group was quite uneven.

More Information

Certain Agreements

All Principal Investigators ARE 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.