A Clinical Trial Investigating Iloprost as Medication to Improve Bone Healing in Patients With Proximal Humeral Fracture

NCT04543682 | Unknown Phase 1 DMC

• 2 other identifiers: SIFU172017-003813-24
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Proximal Humeral Fracture

Keywords

proximal humeral fracture; proximale Humerusfraktur; Ilomedin; Iloprost

Outcome Measures

Primary Outcomes (2)

• Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

  Toxicity grading in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

  12 months

• Efficacy analysis using the Tip Apex Distance (TAD) readout

  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.

  12 weeks after surgery

Secondary Outcomes (6)

• Rate of humeral head necrosis

  12 weeks and 26 weeks after surgery

• 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

• Constant-Murley Score (CMS):

  12 weeks and 26 weeks after surgery

Study Arms (3)

First intervention group (0.125 ng/kg/min Iloprost)

EXPERIMENTAL

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.

Drug: 0.125 ng/kg/min Iloprost; Procedure: open reduction and internal fixation with an angular stable plate (PHILOS)

Second intervention group (0.25 ng/kg/min Iloprost)

EXPERIMENTAL

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.

Drug: 0.25 ng/kg/min Iloprost; Procedure: open reduction and internal fixation with an angular stable plate (PHILOS)

Control intervention group

OTHER

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).

Procedure: open reduction and internal fixation with an angular stable plate (PHILOS)

Interventions

0.125 ng/kg/min Iloprost DRUG

Drug administration through a catheter (inserted at the end of the surgical procedure) begins 24±2 hours after surgery: 0.125 ng/kg/min Iloprost for a duration of 24 hours

Also known as: Ilomedin, SUB08136MIG, CAS (Chemical Abstracts Service) number 78919-13-8

First intervention group (0.125 ng/kg/min Iloprost)

0.25 ng/kg/min Iloprost DRUG

Drug administration through a catheter (inserted at the end of the surgical procedure) begins 24±2 hours after surgery: 0.25 ng/kg/min Iloprost for a duration of 24 hours

Also known as: Ilomedin, SUB08136MIG, CAS number 78919-13-8

Second intervention group (0.25 ng/kg/min Iloprost)

open reduction and internal fixation with an angular stable plate (PHILOS) PROCEDURE

open reduction and internal fixation with an angular stable plate (PHILOS)

Also known as: humerus surgery, Open Reduction and Internal fixation of proximal humeral fracture using Philos plate, PHILOS Plating

Control intervention group; First intervention group (0.125 ng/kg/min Iloprost); Second intervention group (0.25 ng/kg/min Iloprost)

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Center for Muskuloskeletal Surgery, Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Related Publications (12)

• Brorson S, Rasmussen JV, Frich LH, Olsen BS, Hrobjartsson A. Benefits and harms of locking plate osteosynthesis in intraarticular (OTA Type C) fractures of the proximal humerus: a systematic review. Injury. 2012 Jul;43(7):999-1005. doi: 10.1016/j.injury.2011.08.025. Epub 2011 Oct 2.

  PMID: 21968245 BACKGROUND

• DeFranco MJ, Brems JJ, Williams GR Jr, Iannotti JP. Evaluation and management of valgus impacted four-part proximal humerus fractures. Clin Orthop Relat Res. 2006 Jan;442:109-14. doi: 10.1097/01.blo.0000194675.64387.33.

  PMID: 16394748 BACKGROUND

• Khmelnitskaya E, Lamont LE, Taylor SA, Lorich DG, Dines DM, Dines JS. Evaluation and management of proximal humerus fractures. Adv Orthop. 2012;2012:861598. doi: 10.1155/2012/861598. Epub 2012 Dec 18.

  PMID: 23316376 BACKGROUND

• Malavolta EA, Assuncao JH, Pagotto RA, Avelino RL, Gracitelli ME, Pereira CA, Jacomo AL, Ferreira Neto AA. The rotation of the humeral head does not alter radiographic evaluation of the head-shaft angle. J Shoulder Elbow Surg. 2016 Apr;25(4):543-7. doi: 10.1016/j.jse.2015.09.026. Epub 2015 Dec 15.

  PMID: 26700557 BACKGROUND

• Kersten P, White PJ, Tennant A. Is the pain visual analogue scale linear and responsive to change? An exploration using Rasch analysis. PLoS One. 2014 Jun 12;9(6):e99485. doi: 10.1371/journal.pone.0099485. eCollection 2014.

  PMID: 24921952 BACKGROUND

• Balestroni G, Bertolotti G. [EuroQol-5D (EQ-5D): an instrument for measuring quality of life]. Monaldi Arch Chest Dis. 2012 Sep;78(3):155-9. doi: 10.4081/monaldi.2012.121. Italian.

  PMID: 23614330 BACKGROUND

• Hirschmann MT, Wind B, Amsler F, Gross T. Reliability of shoulder abduction strength measure for the Constant-Murley score. Clin Orthop Relat Res. 2010 Jun;468(6):1565-71. doi: 10.1007/s11999-009-1007-3. Epub 2009 Jul 29.

  PMID: 19639370 BACKGROUND

• Conboy VB, Morris RW, Kiss J, Carr AJ. An evaluation of the Constant-Murley shoulder assessment. J Bone Joint Surg Br. 1996 Mar;78(2):229-32.

  PMID: 8666631 BACKGROUND

• Constant CR, Murley AH. A clinical method of functional assessment of the shoulder. Clin Orthop Relat Res. 1987 Jan;(214):160-4.

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• Yian EH, Ramappa AJ, Arneberg O, Gerber C. The Constant score in normal shoulders. J Shoulder Elbow Surg. 2005 Mar-Apr;14(2):128-33. doi: 10.1016/j.jse.2004.07.003.

  PMID: 15789004 BACKGROUND

• Changulani M, Okonkwo U, Keswani T, Kalairajah Y. Outcome evaluation measures for wrist and hand: which one to choose? Int Orthop. 2008 Feb;32(1):1-6. doi: 10.1007/s00264-007-0368-z. Epub 2007 May 30.

  PMID: 17534619 BACKGROUND

• Elazaly H, Dimitriou IM, Maleitzke T, Dahne M, Jaecker V, Maerdian S, Tafelski S, Diekhoff T, Lindner T, Akgun D, Mielke AM, Paksoy A, Amini DA, Planatscher EM, Leopold V, Gonzalez-Khatib S, Kohli PC, Niemann M, Hildebrandt A, Oehme S, Palmowski Y, Paraskevaidis M, Schonnagel L, Braun SB, Pumberger M, Hardt S, Stricker S, Akyuz L, Grutz G, Schaller S, Lauterbach L, Volcksdorff M, Modl L, Textor M, Ort M, Reinke S, Stockle U, Perka C, Duda GN, Schmidt-Bleek K, Geissler S, Winkler T. ILOBONE: A phase I/IIa randomized controlled trial to assess the safety and feasibility of local iloprost therapy for enhancing proximal humerus fracture healing- a pilot study design. J Orthop Surg Res. 2025 May 22;20(1):498. doi: 10.1186/s13018-025-05865-2.

  PMID: 40405317 DERIVED

MeSH Terms

Conditions

Shoulder Fractures

Interventions

Iloprost; Open Fracture Reduction; Fracture Fixation, Internal

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Shoulder Injuries

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Fracture Fixation; Orthopedic Procedures; Therapeutics; Surgical Procedures, Operative

Study Officials

• Tobias Winkler, Prof. Dr.med

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Winkler, Prof.Dr.med

CONTACT

+49 30 450 559 084; tobias.winkler@charite.de

Sven Geissler, Dr. - Ing.

CONTACT

+49 30 450659539; sven.geissler@charite.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med

Model Details: 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).

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 10, 2020
• Study Start: May 12, 2022
• Primary Completion: May 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 3, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)