Clinical Trial Results:
Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis_ A randomised placebo-controller pilot trial
Summary
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EudraCT number |
2012-000748-81 |
Trial protocol |
FI |
Global end of trial date |
01 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Nov 2021
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First version publication date |
14 Nov 2021
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Other versions |
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Summary report(s) |
Main results of the analyses Laboratory analyses of MMP8 and MMP9 in individual subjects in different time points and TIMP-1 Published jouirnal article Individual MMP-levels in each group |
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 |
MMP-Doxi-1
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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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Sponsors
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Sponsor organisation name |
Helsinki University Hospital
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Sponsor organisation address |
Haartmaninkatu 4, Helsinki, Finland,
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Public contact |
Dr Johanna Hästbacka, University of Helsinki, +358 504286701, johanna.hastbacka@hus.fi
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Scientific contact |
Dr Johanna Hästbacka, University of Helsinki, +358 504286701, johanna.hastbacka@hus.fi
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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 |
01 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Jan 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jan 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The feasibility and safety of intravenbous administration of doxycycline in patients with severe sepsis
Determining a dosing regimen that achieve sub-antimicrobial plasma concentrations of doxycycline
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Protection of trial subjects |
The patients received routine intensive care treatment and were treated according to written standard operating procedures in the intensive care unit.
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Background therapy |
The patients received routine intensive care treatment and were treated according to written standard operating procedures in the intensive care unit. | ||
Evidence for comparator |
Comparator was an equivalent volume of placebo (sodium chloride 0.9%) | ||
Actual start date of recruitment |
14 May 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Finland: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
24
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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) |
17
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Please see Figure 1 and methods in attachment | ||||||||||||||||||||
Pre-assignment
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Screening details |
Please see methods and Fig 1 in attached published article | ||||||||||||||||||||
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, Data analyst, Carer, Assessor | ||||||||||||||||||||
Blinding implementation details |
Allocation sheets provided by an external person were saved in a different department in sealed envelopes. A nurse or pharmacist from an unincluded department prepared the study drug and delivered it to the participating department blinded nurse in an opaque syringe labeled with study code.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Doxycycline high dose | ||||||||||||||||||||
Arm description |
Doxyxycline 200mg on first and 100mg on second and third study day, intravenously | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Doxycycline hyclate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use, Solution for infusion
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Dosage and administration details |
Intravenously administrated : arm 1: 200mgx1 day 1, 100mgx1 day 2 and 100mgx1 day 3
arm 2 100mg day 1, 50mgx1 day 2 and 50mg x1 day 3
arm 3 placebo NaCl 09% equivalent volume x1 intravenousely on days 1, 2, and 3
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Arm title
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Doxyxcycline low dose | ||||||||||||||||||||
Arm description |
Doxycycline 100mg on first , and 50mg on second and third study day , once daily, intravenously | ||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||
Investigational medicinal product name |
Doxycycline hyclate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Solution for infusion , Intravenous use
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Dosage and administration details |
Intravenously administrated : arm 1: 200mgx1 day 1, 100mgx1 day 2 and 100mgx1 day 3
arm 2 100mg day 1, 50mgx1 day 2 and 50mg x1 day 3
arm 3 placebo NaCl 09% equivalent volume x1 intravenousely on days 1, 2, and 3
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Investigational medicinal product name |
Doxycycline hyclate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use, Solution for infusion
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Dosage and administration details |
arm 2 100mg day 1, 50mgx1 day 2 and 50mg x1 day 3
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Arm title
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Placebo arm | ||||||||||||||||||||
Arm description |
Sodium chloride 0.9% | ||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||
Investigational medicinal product name |
Natriumchloride Baxter Viaflo 9mg/ml
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Investigational medicinal product code |
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Other name |
Saline
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
50ml infused once daily for three days
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Baseline characteristics reporting groups
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Reporting group title |
Doxycycline high dose
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Reporting group description |
Doxyxycline 200mg on first and 100mg on second and third study day, intravenously | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Doxyxcycline low dose
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Reporting group description |
Doxycycline 100mg on first , and 50mg on second and third study day , once daily, intravenously | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo arm
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Reporting group description |
Sodium chloride 0.9% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
MMP-8-concenbtrations
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Please see attachment file
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Subject analysis set title |
Doxycycline concentrations
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Please see attached file 4
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Subject analysis set title |
Safety and feasibility
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Please see published article, no adverse events were detected during study
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End points reporting groups
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Reporting group title |
Doxycycline high dose
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Reporting group description |
Doxyxycline 200mg on first and 100mg on second and third study day, intravenously | ||
Reporting group title |
Doxyxcycline low dose
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Reporting group description |
Doxycycline 100mg on first , and 50mg on second and third study day , once daily, intravenously | ||
Reporting group title |
Placebo arm
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Reporting group description |
Sodium chloride 0.9% | ||
Subject analysis set title |
MMP-8-concenbtrations
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Please see attachment file
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Subject analysis set title |
Doxycycline concentrations
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Please see attached file 4
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Subject analysis set title |
Safety and feasibility
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Please see published article, no adverse events were detected during study
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End point title |
Doxycycline concentrations after dosing [1] [2] | ||||||||||||||||
End point description |
Plasma doxycycline levels
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End point type |
Primary
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End point timeframe |
24 hours from first dosing
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistics are provided in the attached documents [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The statistics are provided in the attached documents |
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No statistical analyses for this end point |
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End point title |
MMP 8 levels at 24 hours [3] | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
24 hours from dosing
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistics are provided in the attached documents |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Up to 28 days from astudy admissio
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Assessment type |
Non-systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
none | ||
Dictionary version |
x
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Frequency threshold for reporting non-serious adverse events: 5% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no serious adverse events in the study |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
None reported |