Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Five-Year Follow-up of a Prospective Randomized Trial

2018 ◽  
Vol 46 (6) ◽  
pp. 1343-1351 ◽  
Author(s):  
Mats Brittberg ◽  
David Recker ◽  
John Ilgenfritz ◽  
Daniel B.F. Saris ◽  
Keyword(s):  
Clinical Trial ◽  
Informed Consent ◽  
Extension Study ◽  
Cartilage Defects ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
And Function ◽  
Mri Evaluation ◽  
Cultured Chondrocytes

Background: Matrix-based cell therapy improves surgical handling, increases patient comfort, and allows for expanded indications with better reliability within the knee joint. Five-year efficacy and safety of autologous cultured chondrocytes on porcine collagen membrane (MACI) versus microfracture for treating cartilage defects have not yet been reported from any randomized controlled clinical trial. Purpose: To examine the clinical efficacy and safety results at 5 years after treatment with MACI and compare these with the efficacy and safety of microfracture treatment for symptomatic cartilage defects of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This article describes the 5-year follow-up of the SUMMIT (Superiority of MACI Implant Versus Microfracture Treatment) clinical trial conducted at 14 study sites in Europe. All 144 patients who participated in SUMMIT were eligible to enroll; analyses of the 5-year data were performed with data from patients who signed informed consent and continued in the Extension study. Results: Of the 144 patients randomized in the SUMMIT trial, 128 signed informed consent and continued observation in the Extension study: 65 MACI (90.3%) and 63 microfracture (87.5%). The improvements in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain and Function domains previously described were maintained over the 5-year follow-up. Five years after treatment, the improvement in MACI over microfracture in the co-primary endpoint of KOOS pain and function was maintained and was clinically and statistically significant ( P = .022). Improvements in activities of daily living remained statistically significantly better ( P = .007) in MACI patients, with quality of life and other symptoms remaining numerically higher in MACI patients but losing statistical significance relative to the results of the SUMMIT 2-year analysis. Magnetic resonance imaging (MRI) evaluation of structural repair was performed in 120 patients at year 5. As in the 2-year SUMMIT (MACI00206) results, the MRI evaluation showed improvement in defect filling for both treatments; however, no statistically significant differences were noted between treatment groups. Conclusion: Symptomatic cartilage knee defects 3 cm2 or larger treated with MACI were clinically and statistically significantly improved at 5 years compared with microfracture treatment. No remarkable adverse events or safety issues were noted in this heterogeneous patient population.

scholarly journals Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

2021 ◽  
Vol 9 (1) ◽  
pp. 232596712097305
Author(s):  
Hong-Chul Lim ◽  
Yong-Beom Park ◽  
Chul-Won Ha ◽  
Brian J. Cole ◽  
Beom-Koo Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Cartilage Repair ◽  
Older Patients ◽  
Cartilage Defects ◽  
Full Thickness ◽  
Phase 3 ◽  
Randomized Controlled ◽  
Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

scholarly journals Pediatric Tuina For Functional Constipation In Children: Study Protocol For A Randomized Controlled Trail

2021 ◽  
Author(s):  
Xinghe Zhang ◽  
Luan Hu ◽  
Li Li ◽  
Yuanwang Wang ◽  
Can Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Treatment Period ◽  
Functional Constipation ◽  
Gastrointestinal Disorder ◽  
Efficacy And Safety ◽  
Clinical Trial Registry ◽  
Pediatric Tuina ◽  
Randomized Controlled ◽  
Bowel Movements

Abstract Background: Functional constipation (FC) is a common functional gastrointestinal disorder (FGID), which brings many negative impacts to the children’s daily life. Pediatric Tuina has been proved to be a potential therapy for functional constipation (FC). However, the evidence for its effectiveness and safety is insufficient due to the lack of high-quality study. This study aims to evaluate the efficacy and safety of pediatric Tuina for children with FC.Methods/design: This study is a randomized, controlled, multicentre, clinical trial. We will include 176 children with FC from five hospitals. The participants will be randomly allocated into two groups: the pediatric Tuina group and the Medilac-Vita group. This study will include a 1-week actual treatment period and a 2-week follow-up period. Primary outcomes are weekly spontaneous bowel movements (SBMs), weekly complete spontaneous bowel movements (CSBMs). The secondary outcomes are effective rate, stool form, distress sensation, and glycerine enema rate. The assessment will be performed each week. Adverse event will be monitored in treatment period and follow-up period.Discussion: This study is designed to evaluate the efficacy and safety of pediatric Tuina for children with FC, and we hypothesize that pediatric Tuina is more effective than probiotics. It will provide reliable evidence and support for the treatment of FC by pediatric Tuina.Trail registration: This protocol was registered in Chinese Clinical Trial Registry (ChiCTR2100046485).

scholarly journals Evaluation on immediate analgesic efficacy and safety of Kai-Hou-Jian spray (children’s type) in treating sore throat caused by acute pharyngitis and tonsillitis in children: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yan-ning Ma ◽  
Cheng-liang Zhong ◽  
Si-yuan Hu ◽  
Qiu-han Cai ◽  
Sheng-xuan Guo
Keyword(s):  
Clinical Trial ◽  
Sore Throat ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Effective Rate ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acute Pharyngitis ◽  
Randomized Controlled ◽  
Parallel Group

Abstract Background Acute pharyngitis and tonsillitis are common respiratory diseases for which children seek medical care. Their main clinical manifestation is sore throat which interferes with patients’ quality of life. However, there is no proven effective or safe method to treat it. It is necessary to find an excellent strategy to reduce sore throat and reduce the burden of acute illness. We designed the randomized controlled trial with the characteristics of traditional Chinese medicine (TCM) to determine the clinical positioning of Kai-Hou-Jian spray (children’s type) (KHJS) through evidence-based research. This trial aims to evaluate the immediate analgesic efficacy of KHJS on sore throat caused by acute pharyngitis and tonsillitis (wind-heat syndrome/heat exuberance in lung and stomach syndrome) in children and to observe its safety. Methods/design This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. It will include 240 children with acute pharyngitis/tonsillitis from 7 study sites across China. All participants are randomly assigned to two parallel treatment groups, one with KHJS and the other with placebo sprays, for 5 consecutive days. The primary outcome is the time of analgesic onset. Secondary outcomes include duration of analgesic effect, area under time curve of 0–3 h Wong-Baker FACES Pain Rating Scale (WBS) score (AUC0-3 h), rate of analgesic onset, rate of disappearance of sore throat, changes of WBS score (in days), effective rate of pharyngeal signs, and effective rate of TCM syndrome. The incidence of adverse events during the trial is the primary safety outcome. In addition, vital signs and laboratory tests before and after medication are monitored. Discussion To our knowledge, this will be the first clinical trial to explore the immediate analgesic efficacy of a Chinese patent medicine spray for acute pharyngitis/tonsillitis induced sore throat in children in a multicenter, randomized, double-blinded, parallel-group, placebo-controlled manner. Not only might it prove the efficacy and safety of KHJS in the treatment of sore throat caused by acute pharyngitis/tonsillitis in children, but it might also provide evidence for the treatment of acute sore throat with Chinese herbal medicine. Trial registration A multicenter, randomized, double-blind, very low-dose, parallel controlled trial for the immediate analgesic effect and safety of Kai-Hou- Jian spray (children's type) in the treatment of sore throat caused by acute pharyngitis and tonsillitis in children. Chinese Clinical Trial Registry ChiCTR2000031599. Registered on 5 April 2020

scholarly journals Efficacy and safety of duloxetine for postoperative pain after total knee arthroplasty in centrally sensitized patients: study protocol for a randomized controlled trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shicheng Wang ◽  
Wensheng Wang ◽  
Long Shao ◽  
Jing Ling
Keyword(s):  
Clinical Trial ◽  
Total Knee Arthroplasty ◽  
Randomized Controlled Trial ◽  
Pain Control ◽  
Controlled Trial ◽  
Control Group ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Total Knee ◽  
Postoperative Residual

Abstract Background Postoperative residual knee pain after total knee arthroplasty (TKA) is a significant factor that contributes to patient dissatisfaction. Patients with preoperative central sensitization (CS) may be more susceptible to unexplained chronic pain after TKA, and duloxetine has been reported to be effective in post-TKA pain control in patients with CS. However, there remains limited evidence to support this off-label use in routine clinical practice. Hence, we designed this randomized, placebo-controlled, triple-blind clinical trial to evaluate the effects of preoperative screening and targeted duloxetine treatment of CS on postoperative residual pain compared with the care-as-usual control group. Methods This randomized controlled trial includes patients with knee osteoarthritis on a waiting list for primary unilateral TKA. Patients with preoperative CS will be randomly allocated to the perioperative duloxetine treatment group (duloxetine group) or the care-as-usual control group (placebo group). Patients in the duloxetine group will receive a half-dose of preemptive duloxetine (30 mg/day) for a week before surgery and a full-dose of duloxetine (60 mg/day) for six weeks after surgery. The primary outcome is the intensity of residual pain at six months after TKA, including the visual analogue scale, 11-point numeric rating scale, the sensory dimension of the brief pain inventory, and the pain subscale of the Knee injury and Osteoarthritis Outcome Score. The secondary outcome measures will include the pain and function related outcomes. All of the patients will be followed up at one, three, and six months after surgery. All adverse events will be recorded and immediately reported to the primary investigator and ethics committee to decide if the patient needs to drop out from the trial. Discussion This clinical trial will convey the latest evidence of the efficacy and safety of the application of duloxetine in postoperative pain control in CS patients who are scheduled for TKA. The study results will be disseminated at national and international conferences and published in peer-reviewed journals. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn) registration number: ChiCTR2000031674. Registered 07 April 2020.

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