Clinical Trial Results:
Core decompression versus core decompression followed by infusion of Iloprost in the
treatment of non-traumatic avascular necrosis of the femoral head
Summary
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EudraCT number |
2020-000624-20 |
Trial protocol |
DE |
Global end of trial date |
02 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jan 2025
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First version publication date |
03 Jan 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ILONA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
DRKS-ID: DRKS00022404 | ||
Sponsors
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Sponsor organisation name |
Universität Leipzig
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Sponsor organisation address |
Ritterstr. 26, Leipzig, Germany,
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Public contact |
ZKS Leipzig, Universität Leipzig, 49 341 97 16247, ilona@zks.uni-leipzig.de
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Scientific contact |
ZKS Leipzig, Universität Leipzig, 49 341 97 16247, ilona@zks.uni-leipzig.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Nov 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Oct 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Oct 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Primary objective of the ILONA trial is to show that in patients with non-traumatic avascular necrosis of the femoral head treatment with Iloprost for 10 days in addition to core decompression is more effective compared to core decompression alone with regard to functional outcome assessed by the Harris Hip Score (HHS) after 12 months.
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Protection of trial subjects |
In the first 2-3 days of treatment, the individually tolerated dose must be determined.
Blood pressure and heart rate checks are required at the beginning of the infusion and at each dose change (before or at start of new dosage).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 5
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Worldwide total number of subjects |
5
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
5
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study aimed to include a total of 38 patients providing evaluable data on primary and secondary endpoints. During the study period, 17 patients were screened, of which 5 patients were randomized. The first patient was registered for the study on 27.04.2022 and the last patient visit took place on 09.10.2024. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Patients with N-ANFH were pre-screened: After the informed consent, MRI and X-ray images were evaluated by a core lab. If the patient was eligible acc. to the images, further screening took place. | ||||||||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
5 | ||||||||||||||||||||||||
Number of subjects completed |
5 | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Blinding implementation details |
The trial is a double-blind trial. Iloprost was provided by the Sponsor to the trial site pharmacies, placebo was provided by the trial site pharmacies. Blinding was performed by the trial site pharmacy at the time of reconstitution. Blinding was performed following a randomisation list provided by the ZKS Leipzig and the pharmacy staff was instructed on how to perform blinding.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Iloprost | ||||||||||||||||||||||||
Arm description |
patients receiving Iloprost infusion after core decompression | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Iloprost
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Iloprost5 should be administered in a dose of max. 20 μg/day for 10 days.
In the first 2-3 days of treatment, the individually tolerated dose must be determined. The initial treatment should be started with an infusion rate of 0,5 ng/kg/min for half an hour. The dose should then be increased to 0,625 ng/kg/min and to a maximum of 0,75 ng/kg/min. The exact infusion rate, which is calculated based on body weight, should be set to 0,5, 0,625 or 0,75 ng/kg/ml. If side effects such as headaches and nausea or undesirable drop in blood pressure occur, the infusion rate should be reduced until the dose tolerated by the patient has been determined. In case of serious side effects, the infusion should be interrupted. With the tolerated dose determined in the first 2-3 days, treatment should then generally be continued.
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
patients receiving saline solution infusion after core decompression | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Saline Solution (Placebo)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
The placebo is saline solution (0,9%) and the procedures for dosage and administration are identical with iloprost, since the trial is blinded.
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Baseline characteristics reporting groups
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Reporting group title |
Iloprost
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Reporting group description |
patients receiving Iloprost infusion after core decompression | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
patients receiving saline solution infusion after core decompression | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients analysed according to the randomisation result.
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End points reporting groups
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Reporting group title |
Iloprost
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Reporting group description |
patients receiving Iloprost infusion after core decompression | ||
Reporting group title |
Placebo
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Reporting group description |
patients receiving saline solution infusion after core decompression | ||
Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients analysed according to the randomisation result.
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End point title |
Harris Hip Score | ||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
After 12 months (after Core Decompression surgery)
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Notes [1] - one patient dropped out before the documentation of the primary endpoint |
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Statistical analysis title |
reporting of single values | ||||||||||||||||||||||||||||
Statistical analysis description |
Due to the small amount of patients that were recruited, the results are only reported in a descriptive manner.
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Comparison groups |
Iloprost v Placebo v Full analysis set
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Number of subjects included in analysis |
8
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | ||||||||||||||||||||||||||||
P-value |
< 0.05 [3] | ||||||||||||||||||||||||||||
Method |
no tests applicable | ||||||||||||||||||||||||||||
Parameter type |
no parameter applicable | ||||||||||||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0 | ||||||||||||||||||||||||||||
upper limit |
0 | ||||||||||||||||||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0
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Notes [2] - Due to the small amount of patients that were recruited, the results are only reported in a descriptive manner. [3] - The planned tests were not applicable du to the small number of recruited patients. |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were documented on special AE-forms from start of the core decompression surgery until 4 weeks after the last application of Iloprost/placebo.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Iloprost
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Feb 2022 |
documentation of sociodemographic factors added at baseline, evaluation of outcome scores at V1 deleted, since these are evaluated at V2. |
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06 Jun 2023 |
trial indication was expanded from "idiopathic non-traumatic avascular necrosis of the femoral head" to "non-traumatic avascular necrosis of the femoral head". Pathogenesis does not play a determining role in the therapy and outcomes considered in the trila. Thus, the trial indication was no longer restricted to idiopathic pathogenesis and this indication extension was also indicated in the trial title. Restrictions regarding the treated side of the hip (more vs. less effected) were changed. The maximum age for eligible patients was changed from 50 to 65 with the note to rule out the differential diagnosis of rapidly destructive osteoarthritis in patients above 50 years of age. Exclusion criterium "known aetiologies" was changed. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The trial only recruited 5 instead of 38 patients. Therefore, the recruitment was terminated early and the results are only reported in a descriptive manner. |