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

NCT ID: NCT04543682

Last Updated: 2022-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-12

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Proximal Humeral Fracture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

0.125 ng/kg/min Iloprost

Intervention Type 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

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

Intervention Type PROCEDURE

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

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.

Group Type EXPERIMENTAL

0.25 ng/kg/min Iloprost

Intervention Type 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

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

Intervention Type PROCEDURE

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

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).

Group Type OTHER

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

Intervention Type PROCEDURE

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

Interventions

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0.125 ng/kg/min Iloprost

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

Intervention Type DRUG

0.25 ng/kg/min Iloprost

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

Intervention Type DRUG

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

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

Intervention Type PROCEDURE

Other Intervention Names

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Ilomedin SUB08136MIG CAS (Chemical Abstracts Service) number 78919-13-8 Ilomedin SUB08136MIG CAS number 78919-13-8 humerus surgery Open Reduction and Internal fixation of proximal humeral fracture using Philos plate PHILOS Plating

Eligibility Criteria

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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.
Minimum Eligible Age

60 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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Tobias Winkler

Prof. Dr. med

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tobias Winkler, Prof. Dr.med

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

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Center for Muskuloskeletal Surgery, Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Tobias Winkler, Prof.Dr.med

Role: CONTACT

+49 30 450 559 084

Sven Geissler, Dr. - Ing.

Role: CONTACT

+49 30 450659539

Facility Contacts

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Tobias Winkler, PD Dr.

Role: primary

+49 30 450 559 084

References

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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.

Reference Type BACKGROUND
PMID: 21968245 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16394748 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23316376 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26700557 (View on PubMed)

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.

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PMID: 23614330 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19639370 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8666631 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 3791738 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15789004 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17534619 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40405317 (View on PubMed)

Other Identifiers

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2017-003813-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SIFU17

Identifier Type: -

Identifier Source: org_study_id

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