Prospective, Randomized, Phase II, non-Inferiority Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as Adjunct to Hemostasis during Vascular, Hepatic, Soft Tissue, and Spinal Open Surgery
Journal of the American College of Surgeons. 2019
BACKGROUND Thrombin-based formulations have been used for topical hemostasis in surgery for decades. However, the number of randomized clinical trials comparing bovine vs. human thrombin is limited. STUDY DESIGN A randomized, double-blind, non-inferiority phase-II study evaluated the hemostatic efficacy and safety of plasma-derived Topical Thrombin (Human) Grifols (TTH-Grifols) vs. Bovine Thrombin JMI(R) (BT-JMI) (2:1 ratio) in vascular, hepatic, soft tissue, and spinal surgeries. The primary efficacy endpoint was the percentage of patients achieving hemostasis at target bleeding sites with mild-moderate bleeding (response) within 5 minutes (T5) of treatment application. Non-inferiority was met if the lower limit of the 95% CI of the response ratio of TTH-Grifols relative to BT-JMI by T5 exceeded 0.8. Secondary efficacy variables were the cumulative response by 3 and 4 minutes (T3, T4), and the number of treatment failures. Safety parameters were assessed. RESULTS Randomized patients in TTH-Grifols and BT-JMI groups were n=137 and n=68, respectively. In modified intention-to-treat population, rates of hemostasis by T5 were 78.3% (94/120) in TTH-Grifols and 80.3% (49/61) in BT-JMI (response ratio: 0.973; 95% CI: 0.833, 1.135). Rates of hemostasis in vascular, hepatic, soft tissue, and spinal surgeries ranged 75.0%-82.5% for TTH-Grifols, and 54.5%-91.7%, respectively, for BT-JMI. No significant differences in adverse events were observed between treatment groups. Antibodies to bovine factor V antigen were detected in two patients exposed to BT-JMI and in none exposed to TTH-Grifols. CONCLUSIONS TTH-Grifols was safe and well tolerated as a local hemostatic agent and was non-inferior to BT-JMI. No TTH-Grifols-treated patients developed antibodies to thrombin.
Chronic plantar fasciitis: effect of platelet-rich plasma, corticosteroid, and placebo
Plantar fasciitis is a common cause of heel pain. It is a disabling disease in its chronic form. It is a degenerative tissue condition of the plantar fascia rather than an inflammation. Various treatment options are available, including nonsteroidal anti-inflammatory drugs, corticosteroid injections, orthosis, and physiotherapy. This study compared the effects of local platelet-rich plasma, corticosteroid, and placebo injections in the treatment of chronic plantar fasciitis. In this double-blind study, patients were divided randomly into 3 groups. Local injections of platelet-rich plasma, corticosteroid, or normal saline were given. Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot score before injection, at 3 weeks, and at 3-month follow-up. Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up, respectively. Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up, respectively. There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up. There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study. The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis. Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis.