Efficacy of Multimodal Peri- and Intraarticular Drug Injections in Total Knee Arthroplasty

• Sponsor: Asker & Baerum Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00562627
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 3
• Duration (Months): 20
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

Total knee arthroplasty (TKA) is associated with moderate to severe postoperative pain, causing patient discomfort, mobilisation and hospital discharge.

The aim of this study is to:

1. Compare analgetic efficacy of to types of local infiltration analgesia in total knee arthroplasty.

2. Compare analgetic efficacy of local infiltration analgesia with continuous epidural analgesia.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Knee	Drug: ropivacaine; Drug: adrenaline; Drug: ketorolac; Drug: morphine; Drug: fentanyl; Drug: bupivacaine	Phase 4

Detailed Description

Total knee arthroplasty (TKA) is increasingly common in the treatment of knee osteoarthritis. TKA is associated with moderate to severe postoperative pain, causing patient discomfort, mobilisation and hospital discharge.

Continuous epidural analgesia is often used for controlling pain after TKA. Recent studies describe a new method for pain control after total knee arthroplasty which consists of local infiltration with local anesthetics and adrenaline. This infiltrations can be combined with ketorolac and/or morphine. The aim of this study is to:

1. Compare analgetic efficacy of to types of local infiltration analgesia in total knee arthroplasty.

2. Compare analgetic efficacy of local infiltration analgesia with continuous epidural analgesia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Multimodal Peri- and Intraarticular Drug Injections in Total Knee Arthroplasty
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LIA IV Local infiltration analgesia with ropivacaine and adrenaline and intravenous ketorolac and morphine	Drug: ropivacaine; intraoperative and 1. postoperative day; Other Names: Naropin ; Drug: adrenaline; intraoperative LIA (IV and IA) and continuous EDA; Other Names: Adrenalin (epinephrine) ; Drug: ketorolac; intraoperative and 1. postoperative day; Other Names: Toradol ; Drug: morphine; intraoperative; Other Names: Morfin
Experimental: LIA IA Local infiltration analgesia with ropivacaine, adrenaline and ketorolac and morphine	Drug: ropivacaine; intraoperative and 1. postoperative day; Other Names: Naropin ; Drug: adrenaline; intraoperative LIA (IV and IA) and continuous EDA; Other Names: Adrenalin (epinephrine) ; Drug: ketorolac; intraoperative and 1. postoperative day; Other Names: Toradol ; Drug: morphine; intraoperative; Other Names: Morfin
Active Comparator: EDA standard continuous epidural analgesia	Drug: adrenaline; intraoperative LIA (IV and IA) and continuous EDA; Other Names: Adrenalin (epinephrine) ; Drug: fentanyl; continuous postoperatively; Drug: bupivacaine; continuous postoperatively; Other Names: Marcain

Outcome Measures

Primary Outcome Measures

1. Pain at Rest (VAS) [48 hours postoperative]

   VAS (pain at rest) 0-100 mm. VAS 0 mm means no pain and VAS 100 mm means maximal pain.

Secondary Outcome Measures

1. Opioid Use [48 hours postoperative]

   Morphine used by patient controlled analgesia. Amount of used morphine during the first 48 hours after surgery were documented in the CRF by the pain nurses.

2. Time to Readiness for Discharge [up to 10 days postoperative]

   Each postoperative day, discharge readiness was assessed by an orthopaedic surgeon, a pain nurse, a ward nurse, and a physiotherapist according to the following criteria: no evidence for surgical complications, VAS pain at rest ≤30 mm which is controlled by oral analgesics, ability to eat and drink, ability to walk with elbow crutches, and ability to climb ≥8 stairs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• patients at least 18 years of age

• scheduled for elective total knee arthroplasty

• ASA I-III

• signed written informed consent

Exclusion Criteria:

• age < 18

• ASA > III

• moderate or severe cardiac disease, bronchial asthma

• allergy against ropivacaine, ketorolac or morphine

• analgetic abuse

• pregnancy or nursing women

• severe psychiatric disease

• moderate to severe dementia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asker and Baerum Hospital	Rud		Norway	1309

Sponsors and Collaborators

• Asker & Baerum Hospital

Investigators

• Principal Investigator: Ulrich J Spreng, MD, Asker and Baerum Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00562627
• Other Study ID Numbers: 2007-003030-41; EudraCT 2007-003030-41; REK 1.2007.1603
• First Posted: Nov 22, 2007
• Last Update Posted: Aug 8, 2011
• Last Verified: Aug 1, 2011

• Keywords provided by , ,: osteoarthritis; knee arthroplasty; local infiltration analgesia; TKA; epidural analgesia; operation; surgery
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Ketorolac; Epinephrine; Racepinephrine; Fentanyl; Morphine; Bupivacaine; Ropivacaine; Epinephryl borate

Study Results

Participant Flow

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)	LIA IA, (Local Infiltration Analgesia, Intra-articular)	Epidural
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine	Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine	continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml
Period Title: Overall Study
STARTED	34	34	34
COMPLETED	33	33	33
NOT COMPLETED	1	1	1

Baseline Characteristics

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)	LIA IA, (Local Infiltration Analgesia, Intra-articular)	Epidural	Total
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine	Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine	continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml	Total of all reporting groups
Overall Participants	34	34	34	102
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	16 47.1%	14 41.2%	17 50%	47 46.1%
>=65 years	18 52.9%	20 58.8%	17 50%	55 53.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.5 (11)	67.2 (8.9)	65.8 (10.7)	66.5 (9.9)
Sex: Female, Male (Count of Participants)
Female	21 61.8%	21 61.8%	23 67.6%	65 63.7%
Male	13 38.2%	13 38.2%	11 32.4%	37 36.3%
Region of Enrollment (participants) [Number]
Norway	34 100%	34 100%	34 100%	102 100%

Outcome Measures

1. Secondary Outcome

Title	Opioid Use
Description	Morphine used by patient controlled analgesia. Amount of used morphine during the first 48 hours after surgery were documented in the CRF by the pain nurses.
Time Frame	48 hours postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)	LIA IA, (Local Infiltration Analgesia, Intra-articular)	Epidural
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine	Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine	continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml
Measure Participants	33	33	33
Mean (Standard Deviation) [mg]	77 (39)	49 (36)	54 (43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LIA IV (Local Infiltration Analgesia, Intravenous), LIA IA, (Local Infiltration Analgesia, Intra-articular), Epidural
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Pain at Rest (VAS)
Description	VAS (pain at rest) 0-100 mm. VAS 0 mm means no pain and VAS 100 mm means maximal pain.
Time Frame	48 hours postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)	LIA IA, (Local Infiltration Analgesia, Intra-articular)	Epidural
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine	Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine	continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml
Measure Participants	33	33	33
Mean (Standard Deviation) [Units on a scale]	18 (15)	12 (13)	30 (29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LIA IV (Local Infiltration Analgesia, Intravenous), LIA IA, (Local Infiltration Analgesia, Intra-articular), Epidural
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Time to Readiness for Discharge
Description	Each postoperative day, discharge readiness was assessed by an orthopaedic surgeon, a pain nurse, a ward nurse, and a physiotherapist according to the following criteria: no evidence for surgical complications, VAS pain at rest ≤30 mm which is controlled by oral analgesics, ability to eat and drink, ability to walk with elbow crutches, and ability to climb ≥8 stairs.
Time Frame	up to 10 days postoperative

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)	LIA IA, (Local Infiltration Analgesia, Intra-articular)	Epidural
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine	Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine	continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml
Measure Participants	33	33	33
Mean (Standard Deviation) [days]	4 (1.3)	3.5 (0.7)	5.5 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LIA IV (Local Infiltration Analgesia, Intravenous), LIA IA, (Local Infiltration Analgesia, Intra-articular), Epidural
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments

Adverse Events

Arm/Group Title	LIA IV (Local Infiltration Analgesia, Intravenous)		LIA IA, (Local Infiltration Analgesia, Intra-articular)		Epidural
Arm/Group Description	Local infiltration analgesia with 150 mg ropivacaine and 0.5 mg adrenaline and intravenous 30 mg ketorolac and 5mg morphine		Local infiltration analgesia with 150 mg ropivacaine, 0.5 mg adrenaline and 30 mg ketorolac and 5 mg morphine		continuous epidural analgesia with fentanyl 2 ug/ml, bupivacaine 1mg/ml and epinephrine 1 ug/ml
All Cause Mortality
	LIA IV (Local Infiltration Analgesia, Intravenous)		LIA IA, (Local Infiltration Analgesia, Intra-articular)		Epidural
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LIA IV (Local Infiltration Analgesia, Intravenous)		LIA IA, (Local Infiltration Analgesia, Intra-articular)		Epidural
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
Knee infection	0/33 (0%)	0	0/33 (0%)	0	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	LIA IV (Local Infiltration Analgesia, Intravenous)		LIA IA, (Local Infiltration Analgesia, Intra-articular)		Epidural
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

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.