Clinical trial NCT04543682: A Clinical Trial Investigating Iloprost as Medication to Improve Bone Healing in Patients With Proximal Humeral Fracture
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Proximal Humeral Fracture
Keywords: proximal humeral fracture
proximale Humerusfraktur
Ilomedin
Iloprost
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2020-09-10
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized interventional study with parallel groups. Open labeled, add-on controlled study.

In this study, patients will be randomized on a 1:1:1 basis to one of the three arms (two treatment arms and one control arm).
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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 ≤ 2.
* Single, low energy fracture.
* Absence of neurovascular complications at the time of trauma.
* Surgery done within the first 96 hours from injury.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
timeFrame: 12 months
measure: Efficacy analysis using the Tip Apex Distance (TAD) readout
timeFrame: 12 weeks after surgery
Secondary outcomes:
measure: Rate of humeral head necrosis
timeFrame: 12 weeks and 26 weeks after surgery
measure: Humeral head shaft angle
timeFrame: before discharge, 3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery
measure: Pain assessment using the Visual Analogue Scale (VAS)
timeFrame: 24 hours after surgery, before discharge, 3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery
measure: Quality-of-Life (QoL) by applying EQ-5D
timeFrame: 3 weeks, 6 weeks, 12 weeks and 26 weeks after surgery
measure: Constant-Murley Score (CMS):
timeFrame: 12 weeks and 26 weeks after surgery
measure: Disabilities of the Arm, Shoulder and Hand score (DASH)
timeFrame: 12 weeks and 26 weeks after surgery
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Center for Muskuloskeletal Surgery, Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Tobias Winkler, Prof. Dr.med
role: PRINCIPAL_INVESTIGATOR
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