Clinical trial NCT06350565: A Clinical Pharmacological Study of Dose Halving of Dexamethasone in Pregnant Women With Preterm Labour With Preterm Birth at Greater Than or Equal to 34 Gestational Weeks (34GW+)
Official title: A Clinical Pharmacological Study of Dose Halving of Dexamethasone in Pregnant Women With Preterm Labour With Preterm Birth at Greater Than or Equal to 34 Gestational Weeks (34GW+)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Respiratory Distress Syndrome of Newborn
Keywords: Dexamethasone
Pregnancy
Quantitative pharmacology
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2024-04-05
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study plans to conduct a DEX dose halving study and a normal dose study in 34+0-35+6 GW women with preterm preterm labour. In addition, this study plans to conduct a DEX dose halving study and a normal dose study in 34-38+6 GW preterm pregnant women with GDM or diabetic co-pregnancy to explore the feasibility of dose halving in pregnant women with diabetes mellitus.

Detailed description: Two studies will be conducted both of which are single-centre, open clinical studies. It is proposed to collect maternal blood, umbilical vein blood and placental tissue from pregnant women treated with dexamethasone, which excludes early placental detachment, use of surfactant, severe intrauterine haemorrhage, or pregnant women who meet the conditions of the exclusion criteria. Determination and implementation of dexamethasone treatment regimen will be carried out by clinicians in accordance with the treatment guidelines, and the collection of samples will be carried out in the form of opportunistic blood sampling or placenta collection after normal diagnostic and therapeutic operations of pregnant women except for 2 active collections of blood after dosing; this study will not interfere with the normal maternal pregnancy, labour and diagnostic and therapeutic processes.

Half-dose study: A total of 24 Chinese pregnant subjects with 34+0-35+6 GW requiring dexamethasone treatment for preterm labour with preterm prematurity in China were planned to be enrolled in this study. A total of 12 subjects receiving 5 mg dexamethasone (intramuscular injection, q12h, 4 doses) were enrolled in the full-dose group; 12 subjects receiving 2.5 mg dexamethasone (intramuscular injection, q12h, 4 doses) were enrolled in the half-dose group.

EXPLORATORY STUDY: This study was planned to enrol 24 pregnant women with 34+0-38+6 GW preterm labour with confirmed gestational diabetes mellitus (GDM) or diabetes mellitus in combination with pregnancy in a dose exploratory study in this population. A total of 12 subjects were enrolled in the full-dose group to receive 5 mg dexamethasone (intramuscular injection, q12h, 4 doses) and 12 subjects were enrolled in the half-dose group to receive 2.5 mg dexamethasone (intramuscular injection, q12h, 4 doses).

Eligibility criteria: Inclusion Criteria:

Common criteria for half-dose studies and exploratory studies:

1. Age 18-40 years (inclusive);
2. Body mass index (BMI) 18.5-27.9 kg/m2 (inclusive).
3. risk of preterm labour and use of dexamethasone for fetal lung maturation.

Half-dose study-specific criteria:

(1) Greater than or equal to 34+0 gestational weeks and less than or equal to 35+6 gestational weeks at enrolment;

Exploratory study-specific criteria:

1. Greater than or equal to 34+0 gestational weeks and less than or equal to 38+6 gestational weeks at enrolment;
2. Confirmed diagnosis of GDM or having diabetes mellitus.

Exclusion Criteria:

1. Multiple pregnancies (three or more pregnancies)
2. For subjects who are unable to be included in this study in the following cases:
3. Pregnant women with ectopic pregnancy
4. Fetal distress, severe infectious (e.g. sepsis, infectious shock) disease, fever;
5. Those who have taken glucocorticoid drugs within 2 weeks before joining the clinical trial;
6. Those who took clindamycin during the study period;
7. Those with congenital foetal anomalies or foetal hypoxia occurring in early pregnancy;
8. Patients with convulsions;
9. Those with a history of HIV/HCV/hepatitis A, substance abuse;
10. Chorioamnionitis, endometritis;
11. Placental abruption, use of surfactant, severe intrauterine haemorrhage;
12. Pregnant women with cervical dilatation greater than or equal to 4 cm or ultrasonographic neck length greater than or equal to 20 mm;
13. Pregnant women taking food or drugs during the study period that may affect foetal safety;
14. Pregnant women participating in other clinical trials.
15. Gestational diabetes mellitus and patients with diabetes mellitus (exclusion criteria for half-dose studies only).

Primary outcomes:
measure: Respiratory distress syndrome
timeFrame: Detection and evaluation of the newborn within 24 hours of the end of delivery
measure: PK parameters (analysed in conjunction with population pharmacokinetic (PPK) modelling): area under the blood concentration curve, Cmax, Tmax, Kel, t1/2, CL, VZ
timeFrame: 2±0.5 h, 12 h after first dose
measure: Pharmacodynamics
timeFrame: In the course of pregnancy (GW8-delivery), the blood samples were collected every 2 weeks on average, and the blood samples were collected during each delivery and at the time of delivery, and the exact time of delivery was slightly adjusted according to
measure: Measurability indicators
timeFrame: during labour
measure: Blood biochemistry findings in newborns
timeFrame: during labour
measure: DEX potential safety marker test
timeFrame: during labour
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: