Clinical Trial Results:
Intravenous hypertonic saline to lower intraocular pressure in ocular hypertension, primary open-angle glaucoma and exfoliation glaucoma
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Summary
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EudraCT number |
2012-001247-51 |
Trial protocol |
FI |
Global end of trial date |
28 Jan 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Mar 2021
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First version publication date |
24 Mar 2021
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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 |
v.1/040312
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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 Hospital
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Sponsor organisation address |
Haartmaninkatu 4 C, Helsinki, Finland, 00029
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Public contact |
Glaucoma department, Helsinki University Hospital, Eyeclinic, pia.inborr@helsinki.fi
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Scientific contact |
Glaucoma department, Helsinki University Hospital, Eyeclinic, pia.inborr@helsinki.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 |
28 Jan 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Jan 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Jan 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 |
The amount of intraocular pressure reduction 16 minutes after a bolus of intravenous hypertonic saline
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Protection of trial subjects |
The study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board. We required written informed consent from all participants. Patients on oral acetazolamide or with heart or kidney failure, dementia, any other condition that remarkably decreased the patients’ physical performance, ocular surgery within six months, laser cyclophotogoagulation within one week, goniopuncture of Descemet´s membrane, or needling of a filtrating bleb on the same day as IVHTS were ineligible for safety reasons.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Aug 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: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
19
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From 65 to 84 years |
25
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited from the Helsinki University Hospital Glaucoma Department between 1.10.2012 - 28.1.2014. | ||||||||||||
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Pre-assignment
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Screening details |
Eligible to this study were patients with OHT, POAG, and ExG with IOP of 24-30 mmHg who were 25-80 years old. A total of 44 patients gave their consent and completed the study. | ||||||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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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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Ocular hypertension | ||||||||||||
Arm description |
Eligible to this study were patients with ocular hypertension (OHT) with IOP of 24-30 mmHg who were 25-80 years old. OHT patients had no optic nerve head (ONH), retinal nerve fiber layer (RNFL), or visual field (VF) damage, and their untreated IOP was 24-30 mmHg. | ||||||||||||
Arm type |
Active comparator | ||||||||||||
Investigational medicinal product name |
23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
We injected IVHTS (23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland) through a cannulated antecubital vein in the right or left arm. We confirmed the correct intravenous placement of the cannula by injecting 3 ml of physiologic saline. The dosage of IVHTS was 1 mmol/kg sodium chloride in all patients. For a patient who weighed 80 kg, the amount of 23.4% saline was 20 ml, and the infusion rate was 1 ml/s. Thereafter we rinsed the cannula and vein with 5 ml of physiologic saline.
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Arm title
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Primary open angle glaucoma | ||||||||||||
Arm description |
Eligible to this study were patients with primary open angle glaucoma (POAG) with IOP of 24-30 mmHg who were 25-80 years old. POAG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. | ||||||||||||
Arm type |
Active comparator | ||||||||||||
Investigational medicinal product name |
23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
We injected IVHTS (23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland) through a cannulated antecubital vein in the right or left arm. We confirmed the correct intravenous placement of the cannula by injecting 3 ml of physiologic saline. The dosage of IVHTS was 1 mmol/kg sodium chloride in all patients. For a patient who weighed 80 kg, the amount of 23.4% saline was 20 ml, and the infusion rate was 1 ml/s. Thereafter we rinsed the cannula and vein with 5 ml of physiologic saline.
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Arm title
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Exfoliation glaucoma | ||||||||||||
Arm description |
Eligible to this study were patients with exfoliation glaucoma (ExG) with IOP of 24-30 mmHg who were 25-80 years old. ExG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. Patients with ExG had exfoliation material on the lens or pupil margin when examined with biomicroscopy through a dilated pupil. | ||||||||||||
Arm type |
Active comparator | ||||||||||||
Investigational medicinal product name |
23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
We injected IVHTS (23.4% sodium chloride; Natriumklorid Braun 234 mg/ml, B. Braun Medical Oy, Helsinki, Finland) through a cannulated antecubital vein in the right or left arm. We confirmed the correct intravenous placement of the cannula by injecting 3 ml of physiologic saline. The dosage of IVHTS was 1 mmol/kg sodium chloride in all patients. For a patient who weighed 80 kg, the amount of 23.4% saline was 20 ml, and the infusion rate was 1 ml/s. Thereafter we rinsed the cannula and vein with 5 ml of physiologic saline.
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Baseline characteristics reporting groups
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Reporting group title |
Ocular hypertension
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Reporting group description |
Eligible to this study were patients with ocular hypertension (OHT) with IOP of 24-30 mmHg who were 25-80 years old. OHT patients had no optic nerve head (ONH), retinal nerve fiber layer (RNFL), or visual field (VF) damage, and their untreated IOP was 24-30 mmHg. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Primary open angle glaucoma
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Reporting group description |
Eligible to this study were patients with primary open angle glaucoma (POAG) with IOP of 24-30 mmHg who were 25-80 years old. POAG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Exfoliation glaucoma
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Reporting group description |
Eligible to this study were patients with exfoliation glaucoma (ExG) with IOP of 24-30 mmHg who were 25-80 years old. ExG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. Patients with ExG had exfoliation material on the lens or pupil margin when examined with biomicroscopy through a dilated pupil. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Gender
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All women and men patients were analysed separately.
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End points reporting groups
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Reporting group title |
Ocular hypertension
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Reporting group description |
Eligible to this study were patients with ocular hypertension (OHT) with IOP of 24-30 mmHg who were 25-80 years old. OHT patients had no optic nerve head (ONH), retinal nerve fiber layer (RNFL), or visual field (VF) damage, and their untreated IOP was 24-30 mmHg. | ||
Reporting group title |
Primary open angle glaucoma
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Reporting group description |
Eligible to this study were patients with primary open angle glaucoma (POAG) with IOP of 24-30 mmHg who were 25-80 years old. POAG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. | ||
Reporting group title |
Exfoliation glaucoma
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Reporting group description |
Eligible to this study were patients with exfoliation glaucoma (ExG) with IOP of 24-30 mmHg who were 25-80 years old. ExG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. Patients with ExG had exfoliation material on the lens or pupil margin when examined with biomicroscopy through a dilated pupil. | ||
Subject analysis set title |
Gender
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
All women and men patients were analysed separately.
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End point title |
IOP 16 minutes after IVHTS | ||||||||||||||||
End point description |
In our previous study the mean IOP reduction reached its maximum of 9 (SD, 4) mmHg 16 minutes after a 1.0 mmol/kg bolus of 23.4% IVHTS.8 This was used for sample size calculations for this study, and the amount of IOP reduction 16 minutes after the IVHTS bolus was set as the primary outcome measure.
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End point type |
Primary
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End point timeframe |
We measured IOP before giving the IVHTS bolus (baseline), and then every minute for 10 minutes, and at 13, 16, 20, 30, 60, and 120 minutes after the bolus. We measured IOP with a Goldmann applanation tonometer.
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Attachments |
Untitled (Filename: Table 2.docx) |
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Statistical analysis title |
16 min | ||||||||||||||||
Statistical analysis description |
Our data were not normally distributed according to histograms. For comparison of three groups we used the Kruskal-Wallis test, and for paired comparisons the Mann-Whitney U-test. We applied the Bonferroni correction to adjust for multiple testing. For paired data (baseline vs after IVHTS) we used the Wilcoxon signed rank test. Significance was set at P < 0.05. P-values were two-tailed. For statistical analyses we used Stata version 13 (Stata Corp, College Station, TX).
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Comparison groups |
Ocular hypertension v Primary open angle glaucoma v Exfoliation glaucoma
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||
P-value |
< 0.05 [1] | ||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||
Confidence interval |
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| Notes [1] - Significance was set at P < 0.05. P-values were two-tailed. |
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Adverse events information
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Timeframe for reporting adverse events |
We followed patients 2 hours time. Thereafter patients could report significant adverse events by e-mail or phone.
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Adverse event reporting additional description |
The patients were prompted to report if they felt any pain or other sensations during or after the injection, and they graded the amount of pain from 0 to 10; from no pain to the most intolerable pain.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
symptoms | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Ocular hypertension
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Reporting group description |
Eligible to this study were patients with ocular hypertension (OHT) with IOP of 24-30 mmHg who were 25-80 years old. OHT patients had no optic nerve head (ONH), retinal nerve fiber layer (RNFL), or visual field (VF) damage, and their untreated IOP was 24-30 mmHg. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Primary open angle glaucoma
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Reporting group description |
Eligible to this study were patients with primary open angle glaucoma (POAG) with IOP of 24-30 mmHg who were 25-80 years old. POAG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Exfoliation glaucoma
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Reporting group description |
Eligible to this study were patients with exfoliation glaucoma (ExG) with IOP of 24-30 mmHg who were 25-80 years old. ExG patients had glaucomatous thinning of the ONH rim or thinning of the RNFL with corresponding VF defect. Patients with ExG had exfoliation material on the lens or pupil margin when examined with biomicroscopy through a dilated pupil. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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/22834976 |
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