Clinical trial NCT01782885: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: Osteoarthritis
Platelet-Rich Plasma
Intra-articular
Injection
Lead sponsor: Hospital Universitario Dr. Jose E. Gonzalez
Sponsor class: OTHER
First posted: 2013-02-04
Enrollment: 543
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
timeFrame: 0 weeks
measure: Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
timeFrame: 6 weeks
measure: Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
timeFrame: 12 weeks
measure: Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
timeFrame: 24 weeks
Secondary outcomes:
measure: Change in Visual Analog Scale (VAS)
timeFrame: 0-24 weeks
Other outcomes:
measure: Change in SF-12v2 Health Survey
timeFrame: 0 weeks
measure: Change in SF-12v2 Health Survey
timeFrame: 6 weeks
measure: Change in SF-12v2 Health Survey
timeFrame: 12 weeks
measure: Change in SF-12v2 Health Survey
timeFrame: 24 weeks
Locations:
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José E. González
state: Nuevo León
Study officials:
affiliation: Universidad Autónoma de Nuevo León, Facultad de Medicina
name: Mario A. Simental, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Autónoma de Nuevo León, Hospital Universitario Dr. José E. González
name: Felix Vilchez, PhD
role: STUDY_DIRECTOR
affiliation: Universidad Autónoma de Nuevo León, Facultad de Medicina
name: Herminia G Martínez, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.