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CC BY 4.0 · J Knee Surg 2019; 32(11): 1143-1154
DOI: 10.1055/s-0039-1696672
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms

Jack Farr
1   Knee Preservation and Cartilage Restoration Center, OrthoIndy, Indianapolis, Indiana
,
Andreas H. Gomoll
2   Department of Orthopaedic Surgery, Hospital for Special Surgery, New York
,
Adam B. Yanke
3   Section of Cartilage Restoration and Sports Medicine, Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois
,
Eric J. Strauss
4   Department of Orthopaedic Surgery, NYU Langone Medical Center, New York
,
Katie C. Mowry 
5   Department of Research and Development, Organogenesis Inc., Birmingham, Alabama
,
ASA Study Group › Author Affiliations Funding This study was supported by Organogenesis, Inc.
Further Information

Publication History

10 June 2019

03 August 2019

Publication Date:
18 September 2019 (online)

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Correction to:

Erratum to: A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis SymptomsJ Knee Surg 2019; 32(11): e2-e2
DOI: 10.1055/s-0039-3402742

Abstract

Placental-derived tissues are a known source of anti-inflammatory and immune modulating factors. Published pilot data on amniotic suspension allograft (ASA) for the treatment of osteoarthritis (OA) demonstrated safety and trends for improved pain and function. A multicenter randomized controlled trial was designed to evaluate the efficacy of symptom modulation with ASA compared with saline and hyaluronic acid (HA) in subjects with knee OA. A total of 200 subjects were randomized 1:1:1 to ASA, HA, or saline, with subjects blinded to their allocation. Changes from baseline of patient-reported outcomes (PROs)—EQ-5D-5L, Knee Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS), Tegner, and Single Assessment Numerical Evaluation (SANE)—were compared between groups. Patients reporting unacceptable pain at 3 months were considered treatment failures and withdrawn from the study. Statistical analysis was completed by comparing changes in PROs from baseline to 3 and 6 months for all groups. Comparison of demographics between treatment groups showed no significant differences between groups. Patients reporting unacceptable pain at 3 months in each group were ASA (13.2%), HA (68.8%), and saline (75%). Patients receiving ASA demonstrated significantly greater improvements from baseline for overall pain (VAS), KOOS pain, and KOOS-activities of daily living scores compared with those in the HA group (3 months) and both groups (6 months). ASA patients had significantly greater improvements in KOOS symptom scores compared with HA and saline at 3 and 6 months, respectively. OMERACT-OARSI responder rates for ASA, HA, and saline groups were 69.1, 39.1, and 42.6%, respectively (p = 0.0007). Subjects receiving ASA treatment showed greater improvements in PROs and fewer patients reported unacceptable pain compared with HA and saline. The evidence presented in this Level I Randomized Controlled Trial suggests that ASA injection is an effective treatment for the nonoperative management of symptomatic knee OA.

Keywords

osteoarthritis - amniotic membrane - nonoperative management - injection

∗ For details of the ASA Study Group members, please refer the Acknowledgments section provided at the end of the article.


Supplementary Material

 

  • References

  • 1 Cisternas MG, Murphy L, Sacks JJ, Solomon DH, Pasta DJ, Helmick CG. Alternative methods for defining osteoarthritis and the impact on estimating prevalence in a US population-based survey. Arthritis Care Res (Hoboken) 2016; 68 (05) 574-580
    PubMedGoogle Scholar
  • 2 Losina E, Thornhill TS, Rome BN, Wright J, Katz JN. The dramatic increase in total knee replacement size and the obesity epidemic. J Bone Joint Surg Am 2012; 94 (03) 201-207
    CrossrefPubMedGoogle Scholar
  • 3 Van Manen MD, Nace J, Mont MA. Management of primary knee osteoarthritis and indications for total knee arthroplasty for general practitioners. J Am Osteopath Assoc 2012; 112 (11) 709-715
    PubMedGoogle Scholar
  • 4 Hoorntje A, Witjes S, Koenraadt KLM, Aarts R, Weert T, van Geenen RCI. More severe preoperative Kellgren-Lawrence grades of knee osteoarthritis were partially associated with better postoperative patient-reported outcomes in TKA patients. J Knee Surg 2019; 32 (03) 211-217
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Kahn TL, Soheili A, Schwarzkopf R. Outcomes of total knee arthroplasty in relation to preoperative patient-reported and radiographic measures: data from the osteoarthritis initiative. Geriatr Orthop Surg Rehabil 2013; 4 (04) 117-126
    CrossrefPubMedGoogle Scholar
  • 6 American Academy of Orthopaedic Surgeons. Academy A, Aaos. Treatment of osteoarthritis of the knee—evidence-based guidelines. Am Acad Orthop Surg Board Dir 2013 973. Doi: 10.5435/JAAOS-21-09-571
    PubMedGoogle Scholar
  • 7 Farr II J, Miller LE, Block JE. Quality of life in patients with knee osteoarthritis: a commentary on nonsurgical and surgical treatments. Open Orthop J 2013; 7 (05) 619-623
    CrossrefPubMedGoogle Scholar
  • 8 Jones BQ, Covey CJ, Sineath Jr MH. Nonsurgical management of knee pain in adults. Am Fam Physician 2015; 92 (10) 875-883
    PubMedGoogle Scholar
  • 9 Taylor N. Nonsurgical management of osteoarthritis knee pain in the older adult: an update. Rheum Dis Clin North Am 2018; 44 (03) 513-524
    CrossrefPubMedGoogle Scholar
  • 10 Levy DM, Petersen KA, Scalley Vaught M, Christian DR, Cole BJ. Injections for knee osteoarthritis: corticosteroids, viscosupplementation, platelet-rich plasma, and autologous stem cells. Arthroscopy 2018; 34 (05) 1730-1743
    CrossrefPubMedGoogle Scholar
  • 11 McAlindon TE, LaValley MP, Harvey WF. , et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis a randomized clinical trial. JAMA 2017; 317 (19) 1967-1975
    CrossrefPubMedGoogle Scholar
  • 12 Vines JB, Aliprantis AO, Gomoll AH, Farr J. Cryopreserved amniotic suspension for the treatment of knee osteoarthritis. J Knee Surg 2016; 29 (06) 443-450
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis pilot study. Health Qual Life Outcomes 2003; 8: 1-8
    PubMedGoogle Scholar
  • 14 Brittberg M, Recker D, Ilgenfritz J, Saris DBF. ; SUMMIT Extension Study Group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: five-year follow-up of a prospective randomized trial. Am J Sports Med 2018; 46 (06) 1343-1351
    CrossrefPubMedGoogle Scholar
  • 15 Ioppolo F, Saracino F, Rizzo RS. , et al. Comparison between extracorporeal shock wave therapy and intra-articular hyaluronic acid injections in the treatment of first carpometacarpal joint osteoarthritis. Ann Rehabil Med 2018; 42 (01) 92-100
    CrossrefPubMedGoogle Scholar
  • 16 Pham T, van der Heijde D, Altman RD. , et al. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004; 12 (05) 389-399
    CrossrefPubMedGoogle Scholar
  • 17 Chevalier X, Jerosch J, Goupille P. , et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo controlled trial. Ann Rheum Dis 2010; 69 (01) 113-119
    CrossrefPubMedGoogle Scholar
  • 18 Strand V, Baraf HSB, Lavin PT, Lim S, Hosokawa H. A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee. Osteoarthritis Cartilage 2012; 20 (05) 350-356
    CrossrefPubMedGoogle Scholar
  • 19 Aggarwal A, Sempowski IP. Hyaluronic acid injections for knee osteoarthritis. Systematic review of the literature. Can Fam Physician 2004; 50 (Feb): 249-256
    PubMedGoogle Scholar
  • 20 Klocke R, Levasseur K, Kitas GD, Smith JP, Hirsch G. Cartilage turnover and intra-articular corticosteroid injections in knee osteoarthritis. Rheumatol Int 2018; 38 (03) 455-459
    CrossrefPubMedGoogle Scholar
  • 21 Altman RD, Manjoo A, Fierlinger A, Niazi F, Nicholls M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord 2015; 16 (01) 321
    CrossrefPubMedGoogle Scholar
  • 22 Salottolo K, Cole B, Bar-Or D. Intra-articular injection of the anti-inflammatory compound LMWF-5A in adults with severe osteoarthritis: a double-blind prospective randomized controlled multi-center safety and efficacy trial. Patient Saf Surg 2018; 12 (01) 11
    CrossrefPubMedGoogle Scholar
  • 23 Louis ML, Magalon J, Jouve E. , et al. Growth factors levels determine efficacy of platelets rich plasma injection in knee osteoarthritis: a randomized double blind noninferiority trial compared with viscosupplementation. Arthroscopy 2018; 34 (05) 1530-1540.e2
    CrossrefPubMedGoogle Scholar
  • 24 Moatshe G, Morris ER, Cinque ME. , et al. Biological treatment of the knee with platelet-rich plasma or bone marrow aspirate concentrates. Acta Orthop 2017; 88 (06) 670-674
    CrossrefPubMedGoogle Scholar
  • 25 Riboh JC, Saltzman BM, Yanke AB, Fortier L, Cole BJ. Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. Am J Sports Med 2016; 44 (03) 792-800
    CrossrefPubMedGoogle Scholar
  • 26 Shapiro SA, Kazmerchak SE, Heckman MG, Zubair AC, O'Connor MIA. A prospective, single-blind, placebo-controlled trial of bone marrow aspirate concentrate for knee osteoarthritis. Am J Sports Med 2017; 45 (01) 82-90
    CrossrefPubMedGoogle Scholar
  • 27 Spasovski D, Spasovski V, Baščarević Z. , et al. Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis. J Gene Med 2018; 20 (01) e3002
    CrossrefPubMedGoogle Scholar
  • 28 Kon E, Engebretsen L, Verdonk P, Nehrer S, Filardo G. Clinical outcomes of knee osteoarthritis treated with an autologous protein solution injection: a 1-year pilot double-blinded randomized controlled trial. Am J Sports Med 2018; 46 (01) 171-180
    CrossrefPubMedGoogle Scholar
  • 29 Altman RD, Devji T, Bhandari M, Fierlinger A, Niazi F, Christensen R. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: a systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum 2016; 46 (02) 151-159
    CrossrefPubMedGoogle Scholar
  • 30 Saltzman BM, Leroux T, Meyer MA. , et al. The therapeutic effect of intra-articular normal saline injections for knee osteoarthritis: a meta-analysis of evidence level 1 studies. Am J Sports Med 2017; 45 (11) 2647-2653
    CrossrefPubMedGoogle Scholar
  • 31 Devji T, Guyatt GH, Lytvyn L. , et al. Application of minimal important differences in degenerative knee disease outcomes: a systematic review and case study to inform BMJ rapid recommendations. BMJ Open 2017; 7 (05) e015587
    CrossrefPubMedGoogle Scholar
  • 32 Mills KAG, Naylor JM, Eyles JP, Roos EM, Hunter DJ. Examining the minimal important difference of patient-reported outcome measures for individuals with knee osteoarthritis: a model using the Knee injury and Osteoarthritis Outcome Score. J Rheumatol 2016; 43 (02) 395-404
    PubMedGoogle Scholar
  • 33 Gallagher EJ, Liebman M, Bijur PE. Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med 2001; 38 (06) 633-638
    CrossrefPubMedGoogle Scholar
  • 34 Landorf KB, Radford JA, Hudson S. Minimal Important Difference (MID) of two commonly used outcome measures for foot problems. J Foot Ankle Res 2010; 3 (01) 7
    CrossrefPubMedGoogle Scholar
  • 35 McQuilling JP, Vines JB, Kimmerling KA, Mowry KC. Proteomic comparison of amnion and chorion and evaluation of the effects of processing on placental membranes. Wounds 2017; 29 (06) E38-E42
    PubMedGoogle Scholar
  • 36 Goldring MB. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2000; 2 (06) 459-465
    CrossrefPubMedGoogle Scholar
  • 37 Hao Y, Ma DH-K, Hwang DG, Kim W-S, Zhang F. Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea 2000; 19 (03) 348-352
    CrossrefPubMedGoogle Scholar
  • 38 Mori Y, Saito T, Chang SH. , et al. Identification of fibroblast growth factor-18 as a molecule to protect adult articular cartilage by gene expression profiling. J Biol Chem 2014; 289 (14) 10192-10200
    CrossrefPubMedGoogle Scholar
  • 39 Willett NJ, Thote T, Lin AS. , et al. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther 2014; 16 (01) R47
    CrossrefPubMedGoogle Scholar
  • 40 Raines AL, Shih M-S, Chua L, Su CW, Tseng SC, O'Connell J. Efficacy of particulate amniotic membrane and umbilical cord tissues in attenuating cartilage destruction in an osteoarthritis model. Tissue Eng Part A 2017; 23 (1/2): 12-19
    PubMedGoogle Scholar