Jacobs Cale A, Jones Morgan H, Collins Jamie E, Waddell Lily M, Li Xiaojuan, Winalski Carl S, Pietrosimone Brian, Kraus Virginia Byers, Otero Miguel, Wellsandt Elizabeth, Schmitt Laura C, Spindler Kurt P, Anderson Donald D, Rodeo Scott A, Magnussen Robert A, Wolf Brian R, Hart Joe M, Stone Austin V, Conley Caitlin E, Golightly Yvonne M, Myer Gregory D, Snyder-Mackler Lynn, Lotz Martin K, Kim Jason S, McLeod Michelle M, Huebner Janet L, Lisee Caroline, Selzer Faith, Katz Jeffrey N, Long Kyna, Frier Kelly C, Betensky Daniel J, Felson David T, Losina Elena
Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Osteoarthr Cartil Open. 2024 Dec 23;7(1):100563. doi: 10.1016/j.ocarto.2024.100563. eCollection 2025 Mar.
Given the high burden and increasing prevalence of post-traumatic osteoarthritis (PTOA), identifying clinically beneficial strategies to prevent or delay its onset could improve the quality of life of those at high risk of developing the disease.
Preventing Injured Knees from OsteoArthritis: Severity Outcomes (PIKASO) is a multicenter blinded, parallel, two-arm randomized controlled trial of 512 individuals aged 18-45 years undergoing anterior cruciate ligament reconstruction (ACLR). This study is designed to evaluate the efficacy of a 12-month intervention of oral metformin vs. placebo in decreasing the rate of structural knee changes and pain. Participants will be asked to take up to 1500 mg/day of either metformin or placebo as tolerated. The primary outcomes are Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale scores averaged between 12 and 24 months after randomization, and MRI derived cartilage structural change at 24 months. The trial will be deemed successful if at least one of the two primary outcomes reaches the preplanned effect size with sufficient statistical certainty. In this paper, we describe PIKASO elements according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines.
Our multidisciplinary team developed the methods and statistical analysis plan for a placebo controlled, randomized clinical trial to determine whether metformin alters pain and early osteoarthritic changes after ACLR.
This manuscript outlines the rationale, study design, and implementation of the PIKASO trial aiming to prevent the onset of PTOA after ACLR.
clinicaltrials.gov NCT06096259.
鉴于创伤后骨关节炎（PTOA）负担沉重且患病率不断上升，确定预防或延缓其发病的临床有益策略可改善该病高危人群的生活质量。
预防受伤膝关节骨关节炎：严重程度结局（PIKASO）是一项多中心、双盲、平行、双臂随机对照试验，纳入512名年龄在18 - 45岁接受前交叉韧带重建（ACLR）的个体。本研究旨在评估口服二甲双胍与安慰剂进行12个月干预在降低膝关节结构变化率和疼痛方面的疗效。参与者将根据耐受情况服用高达1500毫克/天的二甲双胍或安慰剂。主要结局是随机分组后12至24个月的膝关节损伤和骨关节炎结局评分（KOOS）疼痛子量表评分平均值，以及24个月时MRI得出的软骨结构变化。如果两个主要结局中的至少一个在有足够统计学确定性的情况下达到预先计划的效应大小，则该试验将被视为成功。在本文中，我们根据标准方案项目：干预试验推荐（SPIRIT）指南描述PIKASO的要素。
我们的多学科团队制定了一项安慰剂对照随机临床试验的方法和统计分析计划，以确定二甲双胍是否会改变ACLR后的疼痛和早期骨关节炎变化。
本手稿概述了旨在预防ACLR后PTOA发病的PIKASO试验的原理、研究设计和实施情况。
clinicaltrials.gov NCT06096259。
