TY - JOUR
T1 - Oral enzyme combination with bromelain, trypsin and the flavonoid rutoside reduces systemic inflammation and pain when used pre- and post-operatively in elective total hip replacement
T2 - a randomized exploratory placebo-controlled trial
AU - Vosáhlo, Jiří
AU - Salus, Adam
AU - Smolko, Michael
AU - Němcová, Barbora
AU - Nordmeyer, Veit
AU - Mikles, Milos
AU - Rau, Stefanie M
AU - Erik Johansen, Odd
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Nestlé Health Science (NHSc), the manufacturer of the oral enzyme combination Phlogenzym, which was used in this study. NHSc was involved in study design, data interpretation and writing of the manuscript. Data collection was performed by the Department of Orthopaedics and Traumatology of the Regional Hospital Jihlava, Czech Republic, which received study funding from NHSc. ®
Funding Information:
The authors acknowledge Constantinos Bezos, MCh, of 3 Stories High (3SH), UK, for medical writing support, which was funded by Nestlé Health Science, in accordance with Good Publication Practice guidelines (Ann Intern Med 2022;175:1298-1304). The authors have authorized the submission of the manuscript by 3SH and approved all statements and declarations. We also thank Václav Filip at pharmnet.cz for statistical analysis and statistical advice, funded by Nestlé Health Science. We acknowledge Maximillian von Eynatten from Nestlé Health Science for critical comments, and Pharmnet, the clinical research organization, for operational work. MedDRA trademark is registered by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ®
Publisher Copyright:
© The Author(s), 2023.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - BACKGROUND: Early mobilization after total hip replacement (THR) is key for fast recovery but is often limited by pain. Oral enzyme combinations (OECs) have demonstrated anti-inflammatory and pain-relieving effects.OBJECTIVES AND DESIGN: This prospective, randomized, double-blind, placebo-controlled exploratory trial evaluated the effects of pre- and post-operative use of OEC (90 mg bromelain, 48 mg trypsin, 100 mg rutoside) following elective THR, on post-operative recovery.METHODS: Candidates for primary elective cementless THR owing to osteoarthritis were eligible for participation [age ⩾50 years, body mass index 25-35 kg/m2, C-reactive protein (CRP) ⩽6 mg/L]. Following randomization to OEC or placebo, intervention started pre-operatively and continued onwards until day 42. Main outcomes included post-operative CRP levels (days 1-7), self-reported hip pain at rest (by 0-10 cm visual analogue scale on post-operative days 1-42), post-operative analgesic use [by cumulative analgesic consumption score (CACS) days 7-42], tolerability and adverse events.RESULTS: Patients (N = 34) were recruited from a tertiary orthopaedic hospital in the Czech Republic, of whom 33 completed the study (OEC/placebo: n = 15/18). Baseline characteristics across the groups were comparable. Compared with placebo, the OEC group had numerically lower CRP levels on post-operative days 1-7, including peak level [mean (standard deviation) OEC versus placebo: 81.4 (28.3) versus 106.7 (63.3) mg/L], which translated into a significant 32% lower CRP area under the curve (p = 0.034). The OEC group reported significantly less pain during post-operative days 1-7 versus placebo (analysis of variance treatment × visit [F(4) = 3.989]; p = 0.005). Analgesic use was numerically reduced as assessed through an accumulated CACS. No deleterious effects on haemorheological parameters were observed in either group.CONCLUSIONS: Pre- and post-operative use of OEC significantly reduced CRP levels and patient self-reported pain. OEC may be an efficacious and safe treatment option to facilitate post-operative recovery following THR.TRIAL REGISTRATION: EudraCT number 2016-003078-41.
AB - BACKGROUND: Early mobilization after total hip replacement (THR) is key for fast recovery but is often limited by pain. Oral enzyme combinations (OECs) have demonstrated anti-inflammatory and pain-relieving effects.OBJECTIVES AND DESIGN: This prospective, randomized, double-blind, placebo-controlled exploratory trial evaluated the effects of pre- and post-operative use of OEC (90 mg bromelain, 48 mg trypsin, 100 mg rutoside) following elective THR, on post-operative recovery.METHODS: Candidates for primary elective cementless THR owing to osteoarthritis were eligible for participation [age ⩾50 years, body mass index 25-35 kg/m2, C-reactive protein (CRP) ⩽6 mg/L]. Following randomization to OEC or placebo, intervention started pre-operatively and continued onwards until day 42. Main outcomes included post-operative CRP levels (days 1-7), self-reported hip pain at rest (by 0-10 cm visual analogue scale on post-operative days 1-42), post-operative analgesic use [by cumulative analgesic consumption score (CACS) days 7-42], tolerability and adverse events.RESULTS: Patients (N = 34) were recruited from a tertiary orthopaedic hospital in the Czech Republic, of whom 33 completed the study (OEC/placebo: n = 15/18). Baseline characteristics across the groups were comparable. Compared with placebo, the OEC group had numerically lower CRP levels on post-operative days 1-7, including peak level [mean (standard deviation) OEC versus placebo: 81.4 (28.3) versus 106.7 (63.3) mg/L], which translated into a significant 32% lower CRP area under the curve (p = 0.034). The OEC group reported significantly less pain during post-operative days 1-7 versus placebo (analysis of variance treatment × visit [F(4) = 3.989]; p = 0.005). Analgesic use was numerically reduced as assessed through an accumulated CACS. No deleterious effects on haemorheological parameters were observed in either group.CONCLUSIONS: Pre- and post-operative use of OEC significantly reduced CRP levels and patient self-reported pain. OEC may be an efficacious and safe treatment option to facilitate post-operative recovery following THR.TRIAL REGISTRATION: EudraCT number 2016-003078-41.
UR - http://www.scopus.com/inward/record.url?scp=85166390971&partnerID=8YFLogxK
U2 - 10.1177/1759720X231186875
DO - 10.1177/1759720X231186875
M3 - Journal article
C2 - 37529332
SN - 1759-720X
VL - 15
SP - 1759720X231186875
JO - Therapeutic Advances in Musculoskeletal Disease
JF - Therapeutic Advances in Musculoskeletal Disease
ER -