A Phase I/IIa, Prospective, Mono-center, Randomized, Open Labeled, Controlled Study to Assess the Safety and Efficacy of Applying Iloprost Locally in the Fracture Site to Promote Bone Healing in Patients With Proximal Humeral Fracture
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
研究概览
简要总结
The main objective of this study is to establish the safety as well as the efficacy of local insertion of Iloprost at the fracture site for bone healing of the proximal humeral fracture.
The study will have two treatment groups and one control group. All patients will receive the standard of care procedure (reduction and angular stable (PHILOS) plate fixation). The two treatment groups will additionally be treated with two different Iloprost doses.
Subjects will be assessed for study eligibility within 24h after admission (screening period). Eligible subjects will be assessed for baseline parameters on day 0. Within 96 hours of the study, subjects will undergo surgery, reduction, and angular stable (PHILOS) plate fixation. During the procedure, a catheter will be inserted in the fracture site of the treatment groups in order to deliver the Iloprost locally in the fracture site.
The expected total duration of study participation for each subject comprises 52 weeks, among which 26 weeks include active study participation. At the study end, a telephone call with the subjects will be performed for safety assessment. Recruitment will be completed in approximately 18 months.
Follow up visits following the surgical operation shall take place during weeks 3, 6, 12, and 26. The last follow-up will be a phone call during week 52 for the purpose of safety assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent.
- •Adult male or female subjects between 60 to 80 years old at the time of screening visit.
- •Scheduled Proximal Humerus Internal Locking System (PHILOS) with 3 holes plate length for proximal humerus fracture type 3 or 4 according to Neer classification.
- •Patient with American Society of Anesthesiologists (ASA) score of ≤
- •Single, low energy fracture.
- •Absence of neurovascular complications at the time of trauma.
- •Surgery done within the first 96 hours from injury.
排除标准
- •Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship).
- •Immunosuppression due to illness or medication.
- •Subject with malignancy and undergoing treatment including chemotherapy, radiotherapy or immunotherapy.
- •Known allergies to Iloprost.
- •Conditions where the effects of Iloprost on platelets might increase the risk of haemorrhage (e.g.active peptic ulcers, or intracranial hemorrhage).
- •Severe coronary heart disease or unstable angina; myocardial infarction within the last six months; decompensated cardiac failure if not under close medical supervision; severe arrhythmias; suspected pulmonary congestion; cerebrovascular events (e.g., transient ischaemic attack, stroke) within the last 3 months.
- •Acute or chronic congestive heart failure (NYHA II-IV)
- •Pulmonary hypertension due to venous occlusive disease.
- •Congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension.
- •Subject who is currently enrolled in or has not yet completed a period of at least ( a period of time equal to 5 times as the half-life time of the drug used in the previous trial) since ending other investigational device or drug trial(s).
- •Patients who are dependent on the sponsor, investigator or study site.
- •History of previous proximal humerus surgery on the same side.
- •History of proximal humerus deformity on the same side.
- •Pathological or open fracture.
- •Polytrauma patient.
- •Pregnant or breast-feeding women or women of childbearing potential not protected by an effective contraceptive method of birth control (defined as pearl index < 1).
- •Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel.
- •Patients who are committed to an institution by virtue of an order issued by either the judicial or the administrative authorities.
- •Patients with a history of cerebral circulatory disorders.
- •Patients with any symptomatic or treatable heart disease (including stenting), hypertension treated with a β-receptor blocker, calcium agonists, vasodilator or ACE (Angiotensin-converting-enzyme) inhibitor at more than moderate doses.
研究组 & 干预措施
First intervention group (0.125 ng/kg/min Iloprost)
The first intervention group will receive open reduction and internal fixation with an angular stable plate (PHILOS™ - Depuy Synthes) + Iloprost treatment. Patients will locally receive a dose of 0.125 ng/kg/min of Iloprost over 24 hours via a catheter and an electronic pump system. The catheter will be inserted during the surgical procedure. Infusion of Iloprost will start 24hrs post-operatively and the dose will be delivered over 24h.
干预措施: 0.125 ng/kg/min Iloprost (Drug)
First intervention group (0.125 ng/kg/min Iloprost)
The first intervention group will receive open reduction and internal fixation with an angular stable plate (PHILOS™ - Depuy Synthes) + Iloprost treatment. Patients will locally receive a dose of 0.125 ng/kg/min of Iloprost over 24 hours via a catheter and an electronic pump system. The catheter will be inserted during the surgical procedure. Infusion of Iloprost will start 24hrs post-operatively and the dose will be delivered over 24h.
干预措施: open reduction and internal fixation with an angular stable plate (PHILOS) (Procedure)
Second intervention group (0.25 ng/kg/min Iloprost)
The second intervention group will also receive open reduction and internal fixation with an angular stable plate (PHILOS™ - Depuy Synthes) + Iloprost treatment. Patients will locally receive a dose of 0.25 ng/kg/min of Iloprost over 24 hours via a catheter and an electronic pump system. Infusion will start 24hrs post-operatively and the dose will be delivered over 24h.
干预措施: 0.25 ng/kg/min Iloprost (Drug)
Second intervention group (0.25 ng/kg/min Iloprost)
The second intervention group will also receive open reduction and internal fixation with an angular stable plate (PHILOS™ - Depuy Synthes) + Iloprost treatment. Patients will locally receive a dose of 0.25 ng/kg/min of Iloprost over 24 hours via a catheter and an electronic pump system. Infusion will start 24hrs post-operatively and the dose will be delivered over 24h.
干预措施: open reduction and internal fixation with an angular stable plate (PHILOS) (Procedure)
Control intervention group
Control intervention: Patients will receive the standard of care procedure for such fractures, i.e. standard of care open reduction and internal fixation with an angular stable plate (PHILOS™ - Depuy Synthes).
干预措施: open reduction and internal fixation with an angular stable plate (PHILOS) (Procedure)
结局指标
主要结局
Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
时间窗: 12 months
Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Efficacy analysis using the Tip Apex Distance (TAD) readout
时间窗: 12 weeks after surgery
TAD is an indicator of the progress of fracture healing and the probability of potential complications. Thus, it reflects both the safety and efficacy of the investigational treatment. To evaluate the treatment success rate, we will calculate the percentage loss of the summation of TADs of all locking screws. The value will be classified into one of five ranks as measured after 12 weeks of postoperative follow-up compared to the baseline measurement. For the percentage of original Tip Apex Distance, the sum of the Tip Apex Distance of the humeral head screws will be used: Grade 1: 76%-100% preservation of the original distance (representing the best possible result), Grade 2: 51%-75% preservation of the original distance, Grade 3: 26%-50% preservation of the original distance, Grade 4: 0%-25% preservation of the original distance, and Grade 5: if the patient shows signs of screw protrusion (cut out). Grade 1 will be considered as treatment success, grades 2-5 as treatment failure.
次要结局
- Humeral head shaft angle(before discharge, 3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery)
- Pain assessment using the Visual Analogue Scale (VAS)(24 hours after surgery, before discharge, 3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery)
- Quality-of-Life (QoL) by applying EQ-5D(3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery)
- Rate of humeral head necrosis(12 weeks and 26 weeks after surgery)
- Constant-Murley Score (CMS):(12 weeks and 26 weeks after surgery)
- Disabilities of the Arm, Shoulder and Hand score (DASH)(12 weeks and 26 weeks after surgery)
研究者
Tobias Winkler
Prof. Dr. med
Charite University, Berlin, Germany