Effectiveness of Five Intraarticular Strategies on Knee Osteoarthritis

Assessment of Short-term Effectiveness of Five Local Treatment Modalities in Patients With Symptomatic Knee Osteoarthritis: a Randomized Prospective Study

BACKGROUND: Current medical treatment strategies for knee osteoarthritis (OA) are aimed at pain reduction and symptom control. The Non-Arthroscopic Joint Lavage (NAJL) is included inside the therapeutic algorithm of knee OA when other therapies are contraindicated or have lost effectiveness. The large variety of potentially invasive interventions available (joint lavage included) has raised the need to assess their efficacy. The objective of this study is to compare the short-term effectiveness of five treatment strategies in patients with knee osteoarthritis (OA).

METHODS: It was conducted a randomized prospective study involving 150 patients of whom 76.7% were females. The age range was 40-81 years. All patients had knee OA according to the American College of Rheumatology criteria, with Kellgren-Lawrence radiographic grades II and III. Patients were assigned to five groups, 1) non-arthroscopic joint lavage (NAJL) (n= 30), 2) NAJL plus hyaluronic acid (HA) (n= 32), 3) NAJL plus corticosteroid (CS) (n= 32), 4) HA (n= 31), 5) CS (n= 25). Evaluations took place at baseline, one and three months after enrollment. Demographic variables, Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Lequesne scores were recorded. Statistical analysis included mixed analysis of variance, post-hoc comparisons with Sidak's adjustment, and multiple linear regression using as outcome WOMAC total at 3 months.

TRIAL REGISTRATION: The protocol of the study was approved by the "Hospital Universitario Reina Sofía" Ethics Committee, under the number 1996, in the Minutes 208 of 29 May 2012.

Study Overview

• Status: Completed
• Conditions: Osteo Arthritis Knee
• Intervention / Treatment: Procedure: Non arthroscopic joint lavage; Procedure: Non arthroscopic joint lavage plus corticosteroid; Procedure: Non arthroscopic joint lavage plus hyaluronic acid; Procedure: Intraarticular injection of hyaluronic acid; Procedure: Intraarticular injection of corticosteroid

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meeting American College of Rheumatology (ACR) criteria for knee OA, symptoms for at least three months despite conservative medical treatment, knee OA grade II or III on the radiological Kellgren-Lawrence scale, and voluntary collaboration.

Exclusion Criteria:

• ankylosis of joint;
• total arthroplasty or previous osteotomy
• infected injury;
• treatment with dicumarinic drugs or alterations in blood coagulation,
• venous insufficiency or episode of venous thrombosis;
• administration of hyaluronic acid (HA) in the previous year, and/or corticosteroid (CS) infiltration or NAJL in the previous three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Non arthroscopic joint lavage (NAJL); Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper.	Procedure: Non arthroscopic joint lavage; Instillation of 4 litters of cold physiological serum; Other Names: NAJL
ACTIVE_COMPARATOR: Non arthroscopic joint lavage plus corticosteroid; Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the NAJL plus corticosteroid group was given an intra-articular injection containing 40 mg of triamcinolone acetonide.	Procedure: Non arthroscopic joint lavage plus corticosteroid; Instillation of 4 litters of cold physiological serum followed by intraarticular injection of triamcinolone
ACTIVE_COMPARATOR: Non arthroscopic joint lavage plus hyaluronic acid; Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution, followed by an injection of local anesthetic (5 mL of 2% mepivacaine hydrochloride) into the outer mediopatellar zone. The anesthetic was allowed to act, and an access way was then opened with a No. 16 abocat. Any effusion in the joint was drained. Then, approximately 100 mL of cold saline was instilled through the outer access way. Once the knee was distended, a further 5 mL of local anesthetic was injected into the inner mediopatellar zone, and a new abocat guide was used to establish the inner drainage way. The lavage proper involved instillation of 4 L of cold (8ºC) saline at a constant flow-rate using a dropper line connected to the entry way; the inner zone was also connected to another, free-fall dropper. Following administration of the joint lavage, the patients were given an intra-articular injection containing 4 ml of a bioengineered hyaluronic acid.	Procedure: Non arthroscopic joint lavage plus hyaluronic acid; Instillation of 4 litters of cold physiological serum followed by intraarticular injection of hyaluronic acid
ACTIVE_COMPARATOR: Intraarticular injection of hyaluronic acid; Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.	Procedure: Intraarticular injection of hyaluronic acid; Intraarticular injection containing 4 mL of a bioengineered hyaluronic acid.
ACTIVE_COMPARATOR: Intraarticular injection of corticosteroid; Establishment of sterile areas and cleaning of the skin around the knee with a povidone-iodine solution. This was followed by an intraarticular injection containing 40 mg of triamcinolone acetonide.	Procedure: Intraarticular injection of corticosteroid; Intraarticular injection containing 40 mg of triamcinolone acetonide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC 3.1 Index total	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC total at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lequesne Index	Lequesne Index is a ten question questionnaire that asseses pain and function in patients with osteoarthritis of the knee. It is composed by five questions about pain, being three of them from 0 to 2, and two of them from 0 to 1 point, two questions about maximum distance walked (from 0 to 6 points one and from 0 to 2 the second) and four questions about activities of daily living (from 0 to 2). The total values is the sum of all questions points and range from 1 to 24, being 1-4 mild handicap, 5-7 moderate, 8-10 severe, 11-13 very severe, and >14 extremely severe handicap.	baseline, at one month and at three months
WOMAC 3.1 Index pain	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC pain at baseline
WOMAC 3.1 Index pain	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC pain at one month
WOMAC 3.1 Index pain	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC pain at three months
WOMAC 3.1 Index function	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC function at baseline
WOMAC 3.1 Index function	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC function at one month
WOMAC 3.1 Index function	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC function at three months
WOMAC 3.1 Index stiffness	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC stiffness at baseline
WOMAC 3.1 Index stiffness	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC stiffness at one month
WOMAC 3.1 Index stiffness	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC stiffness at three months
WOMAC 3.1 Index total	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC total at baseline
WOMAC 3.1 Index total	The WOMAC (Western Ontario and McMaster Universities) index is used to assess patients with osteoarthritis of the hip or knee and contains 24 questions, targeting areas of pain, stiffness and physical function. It can be used to monitor the course of the disease or to determine the effectiveness of anti-rheumatic medications. In the study it was used the validated Spanish version of the 5-point adjectival scale format (possible answers are none -0 points-, slight -1 point-, moderate -2 points-, severe -3 points- and extreme -4 points-). The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). WOMAC total is the sum of the three components and it ranges from 0 to 96 points, being 96 the worst outcome.	WOMAC total at one month

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: Lourdes Ladehesa, MD, Hospital Universitario Reina Sofia

Publications and helpful links

General Publications

• Hochberg MC, Altman RD, April KT, Benkhalti M, Guyatt G, McGowan J, Towheed T, Welch V, Wells G, Tugwell P; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012 Apr;64(4):465-74. doi: 10.1002/acr.21596.
• Cope PJ, Ourradi K, Li Y, Sharif M. Models of osteoarthritis: the good, the bad and the promising. Osteoarthritis Cartilage. 2019 Feb;27(2):230-239. doi: 10.1016/j.joca.2018.09.016. Epub 2018 Oct 25.
• Cooper C, Rannou F, Richette P, Bruyere O, Al-Daghri N, Altman RD, Brandi ML, Collaud Basset S, Herrero-Beaumont G, Migliore A, Pavelka K, Uebelhart D, Reginster JY. Use of Intraarticular Hyaluronic Acid in the Management of Knee Osteoarthritis in Clinical Practice. Arthritis Care Res (Hoboken). 2017 Sep;69(9):1287-1296. doi: 10.1002/acr.23204. Epub 2017 Aug 8. No abstract available.
• Escobar A, Quintana JM, Bilbao A, Azkarate J, Guenaga JI. Validation of the Spanish version of the WOMAC questionnaire for patients with hip or knee osteoarthritis. Western Ontario and McMaster Universities Osteoarthritis Index. Clin Rheumatol. 2002 Nov;21(6):466-71. doi: 10.1007/s100670200117.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (ACTUAL): December 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 21, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Corticosteroid; Hyaluronic acid; Joint Lavage
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: NAJL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No