Clinical trial NCT03551509: LifeNet: Extracellular Matrix Graft in Rotator Cuff Repair
Official title: Extracellular Matrix Scaffold Graft Augmentation in Rotator Cuff Repair: a Prospective, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Rotator Cuff Tear
Keywords: Rotator Cuff Tear
Large Rotator Cuff Tear
Massive Rotator Cuff Tear
ECM
Extracellular Matrix
ArthroFLEX
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: LifeNet Health
name: The Cleveland Clinic
First posted: 2018-06-11
Enrollment: 25
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: This trial is to evaluate the effectiveness of the ArthroFLEX® ECM scaffold graph as an augment in rotator cuff repair surgery to reduce the failure rate of rotator cuff repairs for large and massive rotator cuff tears.

Detailed description: This is a prospective, randomized, controlled, multi-center clinical trial to evaluate the effectiveness of an ECM scaffold graft to augment repair of a large/massive rotator cuff tear. The study will involve 70 patients. 35 patients will be randomly assigned to each arm of the study.

Despite advances in surgical technology, repairs of large (3-5 cm) and massive (\>5 cm) rotator cuff tears (RCT) fail between 20%-90% of the time \[1\]. Due to their size and increased structural involvement, large or massive RCT present a substantial challenge to orthopaedic surgeons. \[16\] The repairs tend to fail at the suture-tendon junction, which is due to several factors, including tension at the repair and quality of the tendon \[1-2,5\]. Full thickness tears are uncommon in younger patients, especially those less than forty years old and are usually traumatic in etiology. Younger patients also typically fair better following arthroscopic rotator cuff repair with fewer failures and more successful return to pre-injury level of function \[16\]. One strategy to augment repair of large to massive rotator cuff tears has been the development of biological scaffold materials, which are composed of extracellular matrix (ECM). The ECM composing the scaffolds are made from a number of tissues, including, but not limited to, small intestinal submucosa (SIS), dermis, and pericardium \[3\]. Studies to date include both prospective and retrospective in animal and human models, and include Restore, a porcine-derived SIS by DePuy Orthopaedics, GraftJacket, a human-derived, non-cross-linked dermis graft by Wright Medical Technology, and Zimmer Collagen Repair, a cross-linked porcine derived dermal graft made by Zimmer. Restore studies have shown no benefit and some even an increase in repair failure with recommendations not to use to augment repair. GraftJacket studies have shown a reduction in graft failure; however, several of the Restore and GraftJacket studies are limited by a lack of a control cohort. The Zimmer graft studies have conflicting results with both an improvement and no improvement in failure rates of repair. The prior studies listed are all in vivo; however, the majority are not randomized trials and thus do not have a control with which to compare data. In addition, some trials include open repairs. A lack of prospective, randomized, controlled, in vivo trials exist that evaluate the ability of the ECM scaffold graft augmentation in large to massive arthroscopic rotator cuff repairs to decrease the failure rate.

Eligibility criteria: Inclusion Criteria:

* Patients with a large (3-5 cm) to massive (\>5 cm) rotator cuff tear who will be undergoing open or arthroscopic repair. The cuff tear size will be determined on pre-operative MRI and US.
* Patients who are willing and able to provide written informed consent for their involvement in the study.
* Patients who meet criteria for RCR surgery
* Patients older than 18 years of age

Exclusion Criteria:

* Patients with addiction to illegal drugs, solvents or alcohol who are actively using or have previously attempted and failed a treatment program.
* Patients with bacteremia, a systemic infection, or infection of the surgical site.
* All those who are prisoners.
* Patients who are pregnant or nursing.
* All those with a condition that may limit a patient's ability to finalize the study or that may cause an undue risk to the patient's health and well-being.

Primary outcomes:
measure: Tendon healing
timeFrame: As assessed 1 year postoperatively.
measure: Comparison of healing by MRI vs US
timeFrame: As assessed 1 year postoperatively.
measure: Progress of tendon healing
timeFrame: As assessed at 1 year postoperatively.
Secondary outcomes:
measure: Patient Outcomes: The American Shoulder and Elbow Surgeon Shoulder Score (ASES)
timeFrame: Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery).
measure: Patient Outcomes: The Western Ontario Rotator Cuff Index (WORC)
timeFrame: Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery).
measure: Patient Outcomes: Measurement of Shoulder Activity Level
timeFrame: Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery).
measure: Patient Outcomes: Subjective Shoulder Value (SSV)
timeFrame: Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery).
measure: Patient Outcomes: Constant Score (CS)
timeFrame: Through study completion (1 year after surgery). Specifically this assessment will be administered one time before surgery (during the preoperative examination) and then at every follow-up visit thereafter (6 wks, 3 mos, 6 mos, and 1 year after surgery).
Other outcomes:
Locations:
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
Study officials:
affiliation: Cleveland Clinic Florida
name: Gregory J Gilot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Derwin KA, Badylak SF, Steinmann SP, Iannotti JP. Extracellular matrix scaffold devices for rotator cuff repair. J Shoulder Elbow Surg. 2010 Apr;19(3):467-76. doi: 10.1016/j.jse.2009.10.020. Epub 2010 Feb 26.
citation: Schlegel TF, Hawkins RJ, Lewis CW, Motta T, Turner AS. The effects of augmentation with Swine small intestine submucosa on tendon healing under tension: histologic and mechanical evaluations in sheep. Am J Sports Med. 2006 Feb;34(2):275-80. doi: 10.1177/0363546505279912. Epub 2005 Oct 6.
citation: Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 2009 Jan;5(1):1-13. doi: 10.1016/j.actbio.2008.09.013. Epub 2008 Oct 2.
citation: Sclamberg SG, Tibone JE, Itamura JM, Kasraeian S. Six-month magnetic resonance imaging follow-up of large and massive rotator cuff repairs reinforced with porcine small intestinal submucosa. J Shoulder Elbow Surg. 2004 Sep-Oct;13(5):538-41. doi: 10.1016/j.jse.2004.03.005.
citation: Iannotti JP, Codsi MJ, Kwon YW, Derwin K, Ciccone J, Brems JJ. Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears. A randomized, controlled trial. J Bone Joint Surg Am. 2006 Jun;88(6):1238-44. doi: 10.2106/JBJS.E.00524.
citation: Walton JR, Bowman NK, Khatib Y, Linklater J, Murrell GA. Restore orthobiologic implant: not recommended for augmentation of rotator cuff repairs. J Bone Joint Surg Am. 2007 Apr;89(4):786-91. doi: 10.2106/JBJS.F.00315.
citation: Zheng MH, Chen J, Kirilak Y, Willers C, Xu J, Wood D. Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation. J Biomed Mater Res B Appl Biomater. 2005 Apr;73(1):61-7. doi: 10.1002/jbm.b.30170.
citation: Bond JL, Dopirak RM, Higgins J, Burns J, Snyder SJ. Arthroscopic replacement of massive, irreparable rotator cuff tears using a GraftJacket allograft: technique and preliminary results. Arthroscopy. 2008 Apr;24(4):403-409.e1. doi: 10.1016/j.arthro.2007.07.033.
citation: Badhe SP, Lawrence TM, Smith FD, Lunn PG. An assessment of porcine dermal xenograft as an augmentation graft in the treatment of extensive rotator cuff tears. J Shoulder Elbow Surg. 2008 Jan-Feb;17(1 Suppl):35S-39S. doi: 10.1016/j.jse.2007.08.005.
citation: Soler JA, Gidwani S, Curtis MJ. Early complications from the use of porcine dermal collagen implants (Permacol) as bridging constructs in the repair of massive rotator cuff tears. A report of 4 cases. Acta Orthop Belg. 2007 Aug;73(4):432-6.
citation: Brophy RH, Beauvais RL, Jones EC, Cordasco FA, Marx RG. Measurement of shoulder activity level. Clin Orthop Relat Res. 2005 Oct;439:101-8. doi: 10.1097/01.blo.0000173255.85016.1f.
citation: Parnes N, Bartoszewski NR, Defranco MJ. Arthroscopic Repair of Full-Thickness Rotator Cuff Tears in Active Patients Younger Than 40 Years: 2- to 5-Year Clinical Outcomes. Orthopedics. 2018 Jan 1;41(1):e52-e57. doi: 10.3928/01477447-20171114-02. Epub 2017 Nov 21.
citation: Chung SW, Kim JY, Kim MH, Kim SH, Oh JH. Arthroscopic repair of massive rotator cuff tears: outcome and analysis of factors associated with healing failure or poor postoperative function. Am J Sports Med. 2013 Jul;41(7):1674-83. doi: 10.1177/0363546513485719. Epub 2013 Apr 30.
citation: Greenspoon JA, Petri M, Warth RJ, Millett PJ. Massive rotator cuff tears: pathomechanics, current treatment options, and clinical outcomes. J Shoulder Elbow Surg. 2015 Sep;24(9):1493-505. doi: 10.1016/j.jse.2015.04.005. Epub 2015 Jun 28.