Clinical Trial Results:
Hypertonic saline - the effect of repeating doses
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Summary
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EudraCT number |
2013-001733-41 |
Trial protocol |
FI |
Global end of trial date |
06 Jun 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jun 2024
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First version publication date |
06 Jun 2024
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Other versions |
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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 |
004,1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Helsinki University Central Hospital
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Sponsor organisation address |
Haartmaninkatu 4 C, Helsinki, Finland, 00290
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Public contact |
Department of opthalmology, Helsinki University Central Hospital, +358 503804997, pia.inborr@outlook.com
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Scientific contact |
Department of opthalmology, Helsinki University Central Hospital, +358 503804997, pia.inborr@outlook.com
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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 |
23 Sep 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jun 2014
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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 |
Change in eyepressure after intravenous administration of 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) in two different groups: in Group 1 total dose was 1 mmol/kg and in Group 2 two doses of 0.5 mmol/kg between 10 minutes. We measured before the intravenous hypertonic saline bolus (baseline), 10 and 20 minutes after the single or first bolus, and in Group 2 also 20 minutes after the second bolus.
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Protection of trial subjects |
We excluded patients diagnosed with heart and kidney failure, dementia, or another condition that markedly decreased their physical performance; patients with a history of ocular surgery within six months, laser cyclophotocoagulation within one week or either goniopuncture of Descemet´s membrane or needling of a filtering bleb on the same day as IVHTS; and patients using oral acetazolamide. The study followed the tenets of the Declaration of Helsinki. We required written informed consent from all participants. The study was approved by the institutional review board of the Helsinki University Hospital.
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Background therapy |
We cannulated an antecubital vein in either the right or left arm. We rinsed the cannula with 3 ml physiologic saline to confirm its intravenous position. The IVTHS dose corresponds to a 20 ml injection for an 80 kg patient. We infused the bolus at 1 ml/s, and then rinsed the cannula and vein with physiologic saline using 5 ml after the single bolus and 2.5 ml after both repeated boli. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Sep 2013
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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: 33
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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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) |
11
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
Eligible to our study were patients with an IOP of 22–34 mmHg who were 25–80 years old. We required the patients to be fluent in Finnish or Swedish. We required written informed consent from all participants. | |||||||||
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Pre-assignment
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Screening details |
We measured the IOP with the Goldmann applanation tonometer, and blood pressure and heart rate. We asked the patients to grade the pain at the infusion site on a scale from 0 to 10; zero for no pain, and 10 for the most intense (intolerable) pain. Any other side effect was additionally recorded. | |||||||||
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Period 1
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Period 1 title |
Recruintment (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 | |||||||||
Arm description |
Group 1 received one bolus of 1 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland). | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for suspension for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Group 1 received one bolus of 1 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland). We cannulated an antecubital vein in either the right or left arm. We rinsed the cannula with 3 ml physiologic saline to confirm its intravenous position. The IVTHS dose corresponds to a 20 ml injection for an 80 kg patient. We infused the bolus at 1 ml/s, and then rinsed the cannula and vein with physiologic saline using 5 ml after the single bolus and 2.5 ml after both repeated boli.
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Arm title
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Group 2 | |||||||||
Arm description |
Group 2 received two boli of 0.5 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) with an interval of 10 minutes. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for suspension for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Group 2 received two boli of 0.5 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) with an interval of 10 minutes. We cannulated an antecubital vein in either the right or left arm. We rinsed the cannula with 3 ml physiologic saline to confirm its intravenous position. The IVTHS dose corresponds to a 20 ml injection for an 80 kg patient. We infused the bolus at 1 ml/s, and then rinsed the cannula and vein with physiologic saline using 5 ml after the single bolus and 2.5 ml after both repeated boli.
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Baseline characteristics reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Group 1 received one bolus of 1 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Group 2 received two boli of 0.5 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) with an interval of 10 minutes. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Group 1 received one bolus of 1 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland). | ||
Reporting group title |
Group 2
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Reporting group description |
Group 2 received two boli of 0.5 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) with an interval of 10 minutes. | ||
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End point title |
Group completion | |||||||||
End point description |
In our previous study using the 1.0 mmol/kg bolus, the maximum IOP reduction occurred 10 minutes after the bolus (Inborr et al. 2018). The primary outcome in the present study was the IOP reduction 10 minutes after IVTHS. We compared two different doses, and used a standard deviation (SD) of 2.9 mmHg for power calculation, based on the previous study (Inborr et al. 2018). To show a 3 mmHg difference in IOP reduction with 80% power and 5% significance required at least 12 patients in both groups. We set the group size to 13 patients. We enrolled participants from the Department of Ophthalmology, Helsinki University Hospital, Finland, and continued recruitment until both study groups had at least 13 patients.
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End point type |
Primary
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End point timeframe |
First patient was enrolled to the study 2013-09-26 and last patient 2014-06-06.
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Attachments |
Change in intraocular pressure (median) |
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Statistical analysis title |
Comparison | |||||||||
Statistical analysis description |
The Shapiro-Wilk test was performed to test normal distribution. To compare IOP, BP, HR, and pain grade between the two groups we used the nonparametric Mann-Whitney U test. IOP before and after IVTHS was compared using the Wilcoxon signed-rank test.
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Comparison groups |
Group 1 v Group 2
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Number of subjects included in analysis |
33
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||
Parameter type |
Median difference (final values) | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
During the study; 10 and 20 minutes after the single or first bolus, and in Group 2 also 20 minutes after the second bolus. Patients could contact us also after the study if any adverse events occurred later.
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Adverse event reporting additional description |
We asked the patients to grade the pain at the infusion site on a scale from 0 to 10; zero for no pain, and 10 for the most intense (intolerable) pain. Any other side effect was additionally recorded.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
VAS | ||||||||||||||||||||||||||||||
Dictionary version |
VAS
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Reporting groups
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Reporting group title |
Group 1
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Reporting group description |
Group 1 received one bolus of 1 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland). | ||||||||||||||||||||||||||||||
Reporting group title |
Group 2
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Reporting group description |
Group 2 received two boli of 0.5 mmol/kg 23.4% sodium chloride (Natriumklorid Braun 234 mg/ml, B. Braun Medical, Helsinki, Finland) with an interval of 10 minutes. | ||||||||||||||||||||||||||||||
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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? 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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/35349214 |
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