Comparison of Acetaminophen and PRP Therapy for Knee OA

• ClinicalTrials.gov Identifier: NCT01782885
• Recruitment Status: Completed
• First Posted: February 4, 2013
• Results First Posted: November 20, 2015
• Last Update Posted: November 20, 2015
• Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Information provided by (Responsible Party): Mario Alberto Simental Mendia, M Sc, Principal Investigator, Hospital Universitario Dr. Jose E. Gonzalez

Tracking Information

• First Submitted Date: January 30, 2013
• First Posted Date: February 4, 2013
• Results First Submitted Date: September 21, 2015
• Results First Posted Date: November 20, 2015
• Last Update Posted Date: November 20, 2015
• Study Start Date: May 2013
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2015)

• Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) [ Time Frame: 0 weeks ]
  The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. 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). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
• Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) [ Time Frame: 6 weeks ]
  The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. 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). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
• Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) [ Time Frame: 12 weeks ]
  The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. 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). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
• Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) [ Time Frame: 24 weeks ]
  The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. 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). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.

Original Primary Outcome Measures (submitted: January 31, 2013)

Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) [ Time Frame: 3, 6, 12 months ]

The WOMAC evaluation will be performed on patients who received the treatment at 3,6 and 12 months after treatment finished.

Current Secondary Outcome Measures (submitted: October 19, 2015)

Change in Visual Analog Scale (VAS) [ Time Frame: 0-24 weeks ]

The visual analog scale (VAS) is a psychometric response scale which measures subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their current level of pain by indicating a position along a continuous line of 10 cm. Subject is asked: on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable, what you rate your current pain?

Original Secondary Outcome Measures (submitted: January 31, 2013)

Change in Visual Analog Scale (VAS) [ Time Frame: 3, 6, 12 months ]

The VAS evaluation will be performed on patients who received the treatment at 3,6 and 12 months after treatment finished.

Current Other Pre-specified Outcome Measures (submitted: October 19, 2015)

• Change in SF-12v2 Health Survey [ Time Frame: 0 weeks ]
  The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
• Change in SF-12v2 Health Survey [ Time Frame: 6 weeks ]
  The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
• Change in SF-12v2 Health Survey [ Time Frame: 12 weeks ]
  The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
• Change in SF-12v2 Health Survey [ Time Frame: 24 weeks ]
  The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

Original Other Pre-specified Outcome Measures (submitted: January 31, 2013)

Change in SF-12v2 Health Survey [ Time Frame: 3, 6, 12 months ]

The SF-12v2 Health Survey will be performed on patients who received the treatment at 3,6 and 12 months after treatment finished.

Descriptive Information

• Brief Title: Comparison of Acetaminophen and PRP Therapy for Knee OA
• Official Title: Comparison of Acetaminophen and Platelet-rich Plasma Therapy for the Treatment of Knee Osteoarthritis.

Brief Summary

The purpose of this study is to test whether the platelet-rich plasma (PRP) intra-articular injection therapy is effective as an alternative treatment option in patients with mild knee osteoarthritis within a controlled randomized study compared to first line treatment acetaminophen. The investigators will evaluate patients outcome in level of pain, knee function and quality of life before the treatment and at 6, 12 and 24 weeks follow up.

The study will be complemented with in vitro experiments of human osteoarthritic cartilage explants culture (treated with PRP) for histological and gene expression assays.

PRP intra-articular injections therapy is effective in patients with mild knee osteoarthritis by modifying the biochemical joint environment and cartilage regeneration capability.

Detailed Description

This is a randomized controled study. Patients enroled in the study will be divided into two groups (calculated n=30 per group). One group will be treated with acetaminophen (500 mg/8 h) for 6 weeks, the experimental group will receive a total of 3 intra-articular injections of PRP, one injection every 2 weeks. The intake of any other analgesic or anti-inflammatory drug will be prohibited in patients from two groups.

For those who received the infiltrations, the procedure consist of a 27-mL venous blood sample in 6 vacutainer tubes with sodium citrate 0.109 M for each injection. Samples are gently agitated to ensure mixing the anticoagulant with the blood. An extra tube with anticoagulated EDTA blood is obtained for initial platelet count. Blood samples are centrifuged for 10 minutes at 1800 rpm to separate the erythrocyte layer. The upper plasma layer is carefully collected in a new sterile propylene tube trying not to remove the leukocyte layer. Plasma from all tubes is centrifuged again for 12 minutes at 3400 rpm to obtain a two-part plasma: the upper part consisting on platelet-poor plasma and lower part consisting of platelet-rich plasma (PRP). The platelet-poor plasma is discarded to obtain a final volume of 3 mL. This volume, consisting of PRP, is mixed carefully through pipetting to resuspend platelets and it was then transferred to a new sterile glass tube. An aliquot of the final PRP is sent to the laboratory for platelet count. All open handling sample procedures are performed within a high-efficiency particulate air-filtered laminar flow hood.

Application of injections is carry out after disinfection of skin in the knee joint area. After local anesthesia with lidocaine chlorohydrate, platelets are activated using 10% calcium gluconate solution and the liquid PRP is injected in a sterile condition using a 22 G needle. The needle is inserted using the superolateral approach in an angle of approximately 45°.

Patients from PRP group will be asked to flex and extend their knees immediately after injection so that PRP could distribute adequately across the joint space. After 5-10 minutes of observation the patients are sent home with written indications including to have relative rest 24 to 48 hours after the injection, the use of cold therapy for 15 minutes three times a day and 500 mg of acetaminophen in case of pain and inflammation.

The use of NSAIDs or any steroids is prohibited. All the patients will be evaluated before the beginning of their respective treatment and at 6, 12 and 24 weeks after. Three different scales are used to evaluate clinical outcome, the VAS (Visual Analog Scale) that scores pain level, the WOMAC (Western Ontario and McMaster Universities Arthritis Index) which assesses pain, articular stiffness and functional limitation, and the Spanish (México) version of the SF-12 (Short Form-12) for assessment of quality of life.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Knee Osteoarthritis

Intervention

• Procedure: Intra-articular injection of PRP
  Patients from this arm will receive 3 intra-articular knee injections of autologous platelet-rich plasma, one injection every two weeks (6 weeks total).
• Drug: Acetaminophen
  Patients from this arm will receive a dosis of acetaminophen (500 mg/8 hours) while PRP treatment lasts (6 weeks total).

Study Arms

• Active Comparator: Acetaminophen
  Patients from this arm will receive a dosis of acetaminophen (500 mg/8 hours) while PRP treatment lasts.
  Intervention: Drug: Acetaminophen
• Experimental: Intra-articular injection of PRP
  Patients from this arm will receive 3 intra-articular knee injections of autologous platelet-rich plasma, one injection every two weeks
  Intervention: Procedure: Intra-articular injection of PRP

Publications *

• Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A. Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2012 May;91(5):411-7. doi: 10.1097/PHM.0b013e3182aab72.
• Filardo G, Kon E, Pereira Ruiz MT, Vaccaro F, Guitaldi R, Di Martino A, Cenacchi A, Fornasari PM, Marcacci M. Platelet-rich plasma intra-articular injections for cartilage degeneration and osteoarthritis: single- versus double-spinning approach. Knee Surg Sports Traumatol Arthrosc. 2012 Oct;20(10):2082-91. doi: 10.1007/s00167-011-1837-x. Epub 2011 Dec 28.
• van Buul GM, Koevoet WL, Kops N, Bos PK, Verhaar JA, Weinans H, Bernsen MR, van Osch GJ. Platelet-rich plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes. Am J Sports Med. 2011 Nov;39(11):2362-70. doi: 10.1177/0363546511419278. Epub 2011 Aug 19.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 19, 2015): 543
• Original Estimated Enrollment (submitted: January 31, 2013): 60
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Older than 18 years old
• Patients who haven't received steroids injection or medical treatment 1 month before the study
• Patients with knee osteoarthritis grade I and II (Kellgren-Lawrence scale)
• Indistinct gender
• Patients who accept to participate in the study with previous signed informed consent

Exclusion Criteria:

• Patients with knee osteoarthritis grade III and IV (Kellgren-Lawrence scale)
• Patients with prosthesis
• Pregnancy
• Patients with rheumatic diseases
• Patients with diabetes, hepatic diseases, coagulopathy, cardiovascular diseases, immunosuppression, infections
• Patients taking anticoagulants
• Patients with concentrations of hemoglobin under 11 g/dL and platelets under 150,000/uL

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Mexico

Administrative Information

• NCT Number: NCT01782885
• Other Study ID Numbers: BI13-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mario Alberto Simental Mendia, M Sc, Principal Investigator, Hospital Universitario Dr. Jose E. Gonzalez
• Original Responsible Party: Mario Alberto Simental Mendia, M Sc, Hospital Universitario Dr. Jose E. Gonzalez, M. Sc.
• Current Study Sponsor: Hospital Universitario Dr. Jose E. Gonzalez
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mario A. Simental, MSc; Universidad Autónoma de Nuevo León, Facultad de Medicina
• Study Director: Felix Vilchez, PhD; Universidad Autónoma de Nuevo León, Hospital Universitario Dr. José E. González
• Study Director: Herminia G Martínez, PhD; Universidad Autónoma de Nuevo León, Facultad de Medicina

• PRS Account: Hospital Universitario Dr. Jose E. Gonzalez
• Verification Date: October 2015