Partial Mineralocorticoid DeficiencyPhase 2MINIPREMNCT03001089
Impact of the Administration of Fludrocortisone in Very Premature Infants
A Phase 2 study testing Oral Fludrocortisone (enteral) in people with Partial Mineralocorticoid Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Water and electrolytic homeostasis is remarkably controlled by the mineralocorticoid pathway (renin-angiotensin-aldosterone system acting on the renal tubule). However, the neonatal period in humans is characterized by a reduced ability of the kidney to ensure normal functions of urine concentration and maintenance of… Read more about this study
- Who is it for?
- Ages 26 to 32 weeks
- Conditions the study is for
- Partial Mineralocorticoid Deficiency
- What is being tested?
- Oral Fludrocortisone (enteral)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jun 2017to 8 Sep 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 26 to 32 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Very premature newborns defined by a gestational age <32 and ≥ 26 gestational weeks
- Eutrophic: birth weight between the 10th and 90th percentile of the French reference curves
- Absence of malformations or chromosomal abnormality identified
- Lack of adrenal, pituitary or gonadal diseases diagnosed prior birth
- Lack of participation in another research protocol
- "Inborn": born and hospitalized in the four neonatology departments participating in the study
- Informed consent of the holders of parental authority
Who cannot join
- Maternal treatment prior to pregnancy: systemic or inhaled corticosteroids, hormone therapy for adrenal or pituitary insufficiency, antihypertensive treatment (calcium channel blockers, beta blockers, angiotensin)
- Lack or incomplete treatment of antenatal glucocorticoids (betamethasone)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of the Administration of Fludrocortisone on Fluid and Electrolyte Balance in Very Premature Infants: Pilot Study
Water and electrolytic homeostasis is remarkably controlled by the mineralocorticoid pathway (renin-angiotensin-aldosterone system acting on the renal tubule). However, the neonatal period in humans is characterized by a reduced ability of the kidney to ensure normal functions of urine concentration and maintenance of sodium and water balance. This renal functional immaturity, is associated in the very premature infants (VPT) (born <32 weeks of amenorrhea (SA)) to an immaturity of the adrenal responsible for a default of aldosterone biosynthesis . This relative aldosterone deficiency induces difficulties for VPT to adapt to extra-uterine life when maintaining a positive sodium balance is essential for postnatal growth. The improvement of perinatal care (antenatal corticosteroids maturation, ventilation techniques and use of surfactant) have increased the survival of these children . Nevertheless, extreme prematurity (less than 32 weeks), which concerns nearly 2% of live births in France, remains associated with neurodevelopmental sequelae in nearly 40% of children at 5 years .
Secondary hydroelectrolytic disorders with transient mineralocorticoid adrenal insufficiency is probably one of the factors responsible of these neurological deleterious outcomes as well as the occurrence of other complications (bronchopulmonary dysplasia, enterocolitis necrotizing) of extreme prematurity. Indeed, aside from the administration of antenatal steroids to induce maturation, the prevention of postnatal dehydration reduces the risk of intracranial hemorrhage in that population. However, high fluid intake are associated with an increased incidence of patent ductus arteriosus, of bronchopulmonary dysplasia and necrotizing enterocolitis. This necessitates the evaluation of preventive measures to avoid such fluid and electrolyte imbalances by a pharmacological approach based on mineralocorticoid administration in very premature infants, due to the relative aldosterone deficiency identified in this population.
Read the detailed description
Extreme prematurity affects about 2% of births per year in France and is subject to a significant morbidity and mortality. It is likely that the fluid and electrolyte imbalances associated with mineralocorticoid adrenal insufficiency transient observed in this population of vulnerable newborns contribute to the occurrence of complications that will influence the prognosis medium and long term these children. The expected impact of our pilot study is a direct benefit to the patient, with reduced kidney soda losses from the 3rd day of life and throughout the first week of life (assessed by a non-invasive method: urine collection to compress and measurement of urinary Na / creatinine). This physiological approach (substitution of the deficient hormone) allow better control of sodium and water balance. This could limit a number of common complications of extreme prematurity, occurring in the first weeks of life, such as patent ductus arteriosus, intra-ventricular hemorrhage and bronchopulmonary dysplasia.
The administration of glucocorticoids during the postnatal period (with action both glucocorticoid and mineralocorticoid) enables a reduction in the incidence of bronchopulmonary dysplasia severe. However, such treatment is associated with an increased incidence of neurodevelopmental effects related to activation of the glucocorticoid pathway. Using a specific mineralocorticoid agonist should preserve the beneficial effects without the adverse effects observed. The results of this pilot study will in a second time to consider a clinical trial Phase III national or international evaluating the significant reduction of these complications after substitution by Fludrocortisone the first week of life in the great premature. These results should have a major medical and economic impact. Indeed, neonatal morbidity indicators (intraventricular hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia and enterocolitis necrotizing) are associated with the subsequent development of neurodevelopmental sequelae (cerebral palsy and / or cognitive impairment) at the age of two and five years.
- Conditions
- Partial Mineralocorticoid Deficiency
- Being tested
- Oral Fludrocortisone (enteral), Placebo Oral Tablet
- Keywords
- Neonatology, Endocrinology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Fludrocortisone (enteral)Drug
Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.
Placebo Oral TabletDrug
oral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.
| Study group | Role | What they receive |
|---|---|---|
| Fludrocortisone 10 µg tablets | Active comparator | Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. Receives: Drug: Oral Fludrocortisone (enteral) |
| placebo oral tablet | Placebo comparator | Oral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary sodium loss evaluated by the urinary ratio Na / creatinine
Measurement of Na / urinary creatinine ratio at day 3 (evaluating the efficacity of Fludrocortisone action on the kidney by lowering sodium losses, that are very high in very premature infants) by collection of a urinary spot collected on a gauze compress, placed in the diaper of the newborn.
Measured: day 3 (when urinary sodium losses are at their highest in very premature infants)
Secondary outcomes (14)
Urinary sodium loss evaluated by the urinary ratio Na / creatinine
Measurement of Na / urinary creatinine ratio at day 1, 5, 8, 10 and 15 (evaluating the efficacity of Fludrocortisone action on the kidney by lowering sodium losses, that are very high in very premature infants) by collection of a urinary spot collected on a gauze compress, placed in the diaper of the newborn.
Measured: day1, day5, day8, day10 and day15
urinary sodium and potassium concentrations
Measured: day1,day3, day5, day8, day10 and day15
plasma sodium and potassium concentrations
Measured: day1, day3, day8 et day15
plasma renin concentrations
Measured: day1, day3, day8 et day15
Number of blood tests
Measured: day1,day3, day5, day8, day10 and day15
Neonatal complications
Measured: up to 36 post-conceptional weeks (PCW)
Patent ductus arteriosus (diagnosed by ultrasound)
Measured: Between day2 and day5 and between day7 and day15
Presence of intraventricular hemorrhage (diagnosed by ultrasound)
Measured: between day2 and day5, and between day7 and day15, and at the age of 36 PCW
Oxygen inspired fraction (FiO2)
Measured: At Day 28 and 36 PCW
Blood pressure
Measured: From day1 to day8, at day10, at day15, at one month, three month, six month, twelve month and at 36 PCW
urinary dosage of aldosterone and cortisol
Measured: At one month, three month, six month and twelve month.
urinary index (Aldosterone/Nau)
Measured: day3, day8 and day15
number of days of invasive and non invasive ventilation
Measured: At Day 28 and 36 PCW
weight newborns
Measured: from day1 to day 8, at day 10 and day 15and at 36 PCW
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2016 (estimated)
- Study start1 Jun 2017
- Primary completion8 Sep 2020
- Study completion8 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Partial Mineralocorticoid DeficiencyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martinerie Laetitia, PHD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03001089
- Sponsor's protocol ID
- P150905
- Acronym
- MINIPREM
- Status last verified
- Feb 2021
- First submitted
- 12 Dec 2016
- Last updated
- 16 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of the Administration of Fludrocortisone on Fluid and Electrolyte Balance in Very Premature Infants: Pilot Study
- ClinicalTrials.gov ID
- NCT03001089
- Acronym / sponsor ID
- MINIPREM / P150905
- Conditions
- Partial Mineralocorticoid Deficiency
- Keywords
- Neonatology, Endocrinology
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 8 Sep 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 22 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Water and electrolytic homeostasis is remarkably controlled by the mineralocorticoid pathway (renin-angiotensin-aldosterone system acting on the renal tubule). However, the neonatal period in humans is characterized by a reduced ability of the kidney to ensure normal functions of urine concentration and maintenance of sodium and water balance. This renal functional immaturity, is associated in the very premature infants (VPT) (born <32 weeks of amenorrhea (SA)) to an immaturity of the adrenal responsible for a default of aldosterone biosynthesis . This relative aldosterone deficiency induces difficulties for VPT to adapt to extra-uterine life when maintaining a positive sodium balance is essential for postnatal growth. The improvement of perinatal care (antenatal corticosteroids maturation, ventilation techniques and use of surfactant) have increased the survival of these children . Nevertheless, extreme prematurity (less than 32 weeks), which concerns nearly 2% of live births in France, remains associated with neurodevelopmental sequelae in nearly 40% of children at 5 years .
Secondary hydroelectrolytic disorders with transient mineralocorticoid adrenal insufficiency is probably one of the factors responsible of these neurological deleterious outcomes as well as the occurrence of other complications (bronchopulmonary dysplasia, enterocolitis necrotizing) of extreme prematurity. Indeed, aside from the administration of antenatal steroids to induce maturation, the prevention of postnatal dehydration reduces the risk of intracranial hemorrhage in that population. However, high fluid intake are associated with an increased incidence of patent ductus arteriosus, of bronchopulmonary dysplasia and necrotizing enterocolitis. This necessitates the evaluation of preventive measures to avoid such fluid and electrolyte imbalances by a pharmacological approach based on mineralocorticoid administration in very premature infants, due to the relative aldosterone deficiency identified in this population.
Detailed description
Extreme prematurity affects about 2% of births per year in France and is subject to a significant morbidity and mortality. It is likely that the fluid and electrolyte imbalances associated with mineralocorticoid adrenal insufficiency transient observed in this population of vulnerable newborns contribute to the occurrence of complications that will influence the prognosis medium and long term these children. The expected impact of our pilot study is a direct benefit to the patient, with reduced kidney soda losses from the 3rd day of life and throughout the first week of life (assessed by a non-invasive method: urine collection to compress and measurement of urinary Na / creatinine). This physiological approach (substitution of the deficient hormone) allow better control of sodium and water balance. This could limit a number of common complications of extreme prematurity, occurring in the first weeks of life, such as patent ductus arteriosus, intra-ventricular hemorrhage and bronchopulmonary dysplasia.
The administration of glucocorticoids during the postnatal period (with action both glucocorticoid and mineralocorticoid) enables a reduction in the incidence of bronchopulmonary dysplasia severe. However, such treatment is associated with an increased incidence of neurodevelopmental effects related to activation of the glucocorticoid pathway. Using a specific mineralocorticoid agonist should preserve the beneficial effects without the adverse effects observed. The results of this pilot study will in a second time to consider a clinical trial Phase III national or international evaluating the significant reduction of these complications after substitution by Fludrocortisone the first week of life in the great premature. These results should have a major medical and economic impact. Indeed, neonatal morbidity indicators (intraventricular hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia and enterocolitis necrotizing) are associated with the subsequent development of neurodevelopmental sequelae (cerebral palsy and / or cognitive impairment) at the age of two and five years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fludrocortisone 10 µg tablets | Active comparator | Drug: Oral Fludrocortisone (enteral)Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. |
| placebo oral tablet | Placebo comparator | Drug: Placebo Oral TabletOral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. |
Who may qualify
- Ages
- 26 to 32 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Very premature newborns defined by a gestational age <32 and ≥ 26 gestational weeks
- Eutrophic: birth weight between the 10th and 90th percentile of the French reference curves
- Absence of malformations or chromosomal abnormality identified
- Lack of adrenal, pituitary or gonadal diseases diagnosed prior birth
- Lack of participation in another research protocol
Key exclusion criteria (2 listed)
- Maternal treatment prior to pregnancy: systemic or inhaled corticosteroids, hormone therapy for adrenal or pituitary insufficiency, antihypertensive treatment (calcium channel blockers, beta blockers, angiotensin)
- Lack or incomplete treatment of antenatal glucocorticoids (betamethasone)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Fludrocortisone (enteral)Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. | Drug | Fludrocortisone 10 µg tablets |
| Placebo Oral Tabletoral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8. | Drug | placebo oral tablet |
Primary outcome
Urinary sodium loss evaluated by the urinary ratio Na / creatinine
Time frame: day 3 (when urinary sodium losses are at their highest in very premature infants)
Measurement of Na / urinary creatinine ratio at day 3 (evaluating the efficacity of Fludrocortisone action on the kidney by lowering sodium losses, that are very high in very premature infants) by collection of a urinary spot collected on a gauze compress, placed in the diaper of the newborn.
14 secondary outcomes
Urinary sodium loss evaluated by the urinary ratio Na / creatinine
Time frame: day1, day5, day8, day10 and day15
urinary sodium and potassium concentrations
Time frame: day1,day3, day5, day8, day10 and day15
plasma sodium and potassium concentrations
Time frame: day1, day3, day8 et day15
plasma renin concentrations
Time frame: day1, day3, day8 et day15
Number of blood tests
Time frame: day1,day3, day5, day8, day10 and day15
Neonatal complications
Time frame: up to 36 post-conceptional weeks (PCW)
Patent ductus arteriosus (diagnosed by ultrasound)
Time frame: Between day2 and day5 and between day7 and day15
Presence of intraventricular hemorrhage (diagnosed by ultrasound)
Time frame: between day2 and day5, and between day7 and day15, and at the age of 36 PCW
Oxygen inspired fraction (FiO2)
Time frame: At Day 28 and 36 PCW
Blood pressure
Time frame: From day1 to day8, at day10, at day15, at one month, three month, six month, twelve month and at 36 PCW
urinary dosage of aldosterone and cortisol
Time frame: At one month, three month, six month and twelve month.
urinary index (Aldosterone/Nau)
Time frame: day3, day8 and day15
number of days of invasive and non invasive ventilation
Time frame: At Day 28 and 36 PCW
weight newborns
Time frame: from day1 to day 8, at day 10 and day 15and at 36 PCW
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2021.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martinerie Laetitia, PHD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral Fludrocortisone (enteral) in people with Partial Mineralocorticoid Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urinary sodium loss evaluated by the urinary ratio Na / creatinine (time frame: day 3 (when urinary sodium losses are at their highest in very premature infants)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2021.