Clinical Trial Results:
Correction of Neonatal Glutathione by N-acetylcysteine in Pregnant Women at Risk of Premature Birth (GSH MAP)
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Summary
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EudraCT number |
2017-003999-31 |
Trial protocol |
FR |
Global end of trial date |
01 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Sep 2023
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First version publication date |
09 Sep 2023
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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 |
RC15_0476
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03596125 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CHU Nantes
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Sponsor organisation address |
5 allée de l'île Gloriette, Nantes, France, 44000
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Public contact |
Direction Recherche CHU de Nantes, CHU de Nantes, 0033 2 40 08 49 8, soizic.boinet@chu-nantes.fr
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Scientific contact |
Direction Recherche CHU de Nantes, CHU de Nantes, 0033 2 40 08 49 8, soizic.boinet@chu-nantes.fr
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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 |
03 Jul 2023
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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 |
01 Nov 2021
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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 |
The main objective of this project is to determine whether N-acetyl-cysteine supplementation in women with moderate or severe Threatened Premature Delivery corrects fetal blood glutathione deficiency at birth.
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Protection of trial subjects |
Eligible patients are mothers admitted to Nantes University Hospital with severe or moderate MAP between 24 and 34 weeks' gestation. Following information, informed maternal consent after sufficient time for reflection, and inclusion in the study, patients will receive the treatment determined by randomisation.
As part of the study, patients will be monitored for the duration of NAC supplementation and until delivery, with collection of a venous cord blood sample to measure GSH (primary endpoint).
However, for reasons of safety and vigilance, the patient will be monitored until 72 hours post-partum. In the event of transfer to another neonatology unit, monitoring should be continued by regular telephone contact with the peripheral hospital centre. Overall neonatal follow-up (via the hospitalisation report) will then be carried out by the investigation team in order to collate pathologies of interest within the framework of GSH-MAP: ECUN, SDR/DBP, retinopathy, HIV, etc.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Nov 2018
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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 |
France: 39
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Worldwide total number of subjects |
39
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EEA total number of subjects |
39
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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) |
39
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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 |
Pregnant patients diagnosed with severe or moderate MAP between 24 and 34 weeks' gestation who are over 18 years of age and who are being followed in the obstetrics department of the CHU de Nantes will be recruited after receiving a full explanation of the aims of the GSH-MAP research, as well as the potential benefits and risks of the protocol. | |||||||||
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Pre-assignment
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Screening details |
Subjects were included in Nantes Hospital | |||||||||
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Period 1
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Period 1 title |
Periode 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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N-Acetylcystéine | |||||||||
Arm description |
Injectable NAC was administered only for severe MAP. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
n-acetylcystéine 1.5g/250mL
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Injection
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Dosage and administration details |
Severe MAP patients will receive N-acetylcysteine in the form of an IV test bolus (1.5 g) over 1 hour, followed by an IV loading dose (7.5 g) over 4 hours and, finally, a maintenance dose -per os- of 6g per day for 7 days and a relay dose of 1.8g per day up to 37 weeks' gestation.
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Investigational medicinal product name |
n-acetylcystéine 7.5g/500mL
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Injection
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Dosage and administration details |
Severe MAP patients will receive N-acetylcysteine in the form of an IV test bolus (1.5 g) over 1 hour, followed by an IV loading dose (7.5 g) over 4 hours and, finally, a maintenance dose -per os- of 6g per day for 7 days and a relay dose of 1.8g per day up to 37 weeks' gestation.
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Investigational medicinal product name |
N acetylcystéine 600mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Severe MAP patients will receive N-acetylcysteine in the form of an IV test bolus (1.5 g) over 1 hour, followed by an IV loading dose (7.5 g) over 4 hours and, finally, a maintenance dose -per os- of 6g per day for 7 days and a relay dose of 1.8g per day up to 37 weeks' gestation.
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Arm title
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Placebo | |||||||||
Arm description |
Injectable placebo was administered only for severe MAP. | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
GLUCIDION G5
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Injection
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Dosage and administration details |
Injectable placebo will only be administered in cases of severe MAP.
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Investigational medicinal product name |
Placebo comprimé blanc dragéifié (COOPER)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Moderate MAP patients will receive an oral placebo
The per os switch will be made with the first meal following interruption of the IV route, with a minimum delay of 4 hours.
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Baseline characteristics reporting groups
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Reporting group title |
N-Acetylcystéine
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Reporting group description |
Injectable NAC was administered only for severe MAP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Injectable placebo was administered only for severe MAP. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
all patients randomized without violation of inclusion criteria.
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
- meeting all inclusion/non-inclusion criteria
- with at least 7 days of treatment (exclusion of 8 patients, ident. 3, 6 ,13, 17, 28, 31, 34, 37)
- with venous cord blood sampling at delivery (4 exclusions, ident. 7, 11, 33, 39)
- having taken the requested dose within the first 7 days (2 exclusions, ident. 2 and 10)
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End points reporting groups
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Reporting group title |
N-Acetylcystéine
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Reporting group description |
Injectable NAC was administered only for severe MAP. | ||
Reporting group title |
Placebo
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Reporting group description |
Injectable placebo was administered only for severe MAP. | ||
Subject analysis set title |
FAS
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
all patients randomized without violation of inclusion criteria.
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Subject analysis set title |
Per protocol
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
- meeting all inclusion/non-inclusion criteria
- with at least 7 days of treatment (exclusion of 8 patients, ident. 3, 6 ,13, 17, 28, 31, 34, 37)
- with venous cord blood sampling at delivery (4 exclusions, ident. 7, 11, 33, 39)
- having taken the requested dose within the first 7 days (2 exclusions, ident. 2 and 10)
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End point title |
glutathione concentration (GSH reduced form) in red blood cells from venous cord blood collected at birth | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
at birth
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Statistical analysis title |
efficacité | ||||||||||||
Comparison groups |
N-Acetylcystéine v Placebo
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Number of subjects included in analysis |
39
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
7th day post partum or hospital discharge
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
All patient randomized
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Reporting group description |
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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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15 Mar 2019 |
Modification of inclusion criteria |
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01 Apr 2020 |
Changes to RCP
Extension
Change number of subjects |
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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. | |||
| None reported | |||
