Ignite Creation Date:
2024-07-17 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06463652
Status:
RECRUITING
Last Update Posted:
2024-07-11
First Post:
2024-06-07
Brief Title:
Cerclage with Progesterone Versus Progesterone Only in Singleton Pregnancies
Sponsor:
Mỹ Đức Hospital
Organization:
Mỹ Đức Hospital
Study Overview
Official Title:
Cervical Cerclage with Vaginal Progesterone Versus Vaginal Progesterone Only for Preterm Birth Prevention in Women with a Singleton Pregnancy and a Short Cervical Length a Randomized Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESILIENT
Brief Summary:
This study compares the effectiveness of cervical cerclage with vaginal progesterone to vaginal progesterone only for the prevention of preterm birth in women with a singleton pregnancy and a short cervical length Participants will be randomly assigned in a 11 ratio to receive cerclage plus progesterone or progesterone only
Detailed Description:
This open-label multi-center randomized controlled trial aims to compare the effectiveness of cervical cerclage with vaginal progesterone the combined therapy group to vaginal progesterone only the progesterone-only group for the prevention of preterm birth in women with a singleton pregnancy and a cervical length 25mm
After written informed consent women will be randomly assigned in a 11 ratio to receive a cervical cerclage with vaginal progesterone or vaginal progesterone only Randomization will be carried out by entering participant details into HOPE Epi a web portal of HOPE Research Center My Duc Hospital Treatment allocation will be assigned according to a computer-generated randomization list stored in the online system with a permuted random block size of 2 4 or 6 Blinding will not be possible due to the nature of interventions However neonatologists assessing the neonates will be unaware of treatment allocation Apart from randomization participants will be monitored and treated according to local protocol
All women at 16 07 to 24 07 weeks gestation with a singleton pregnancy will undergo cervical length measurement and digital examination at screening routinely Women with a cervical length 25 mm will be eligible for the study Eligible women will further undergo a speculum examination to assess the feasibility of treatment with either cervical cerclage or vaginal progesterone and to exclude premature rupture of the membranes acute vaginitis and cervicitis Only women in whom the clinician assesses both treatments as feasible will be randomized
Women allocated to a combined therapy group will receive the intervention according to local protocol within a week after randomization Briefly cervical cerclage McDonald technique will be performed in the operation theatre From the same day of undergoing cerclage participants will be receiving 200 mg vaginal progesterone purchased from the manufacturer Cyclogest 200mg Actavis United Kingdom once daily at bedtime Participants will be asked to record their drug application in a participant diary sheet
Women allocated to the progesterone-only group will be receiving 200 mg vaginal progesterone purchased from the manufacturer Cyclogest 200mg Actavis United Kingdom once daily at bedtime Participants will be asked to record their drug application in a participant diary sheet
In both groups interventions will be stopped at 37 07 weeks of gestation or at delivery
Primary analysis will be performed on an intention-to-treat basis The primary outcome the time from randomization to delivery will be summarised as median and IQR and compared between the two arms using the Mann-Whitney test A mean ratio with a 95 confidence interval will be calculated to assess the effect of the treatment Kaplan-Meier and Cox proportional hazard analysis will be performed in which the gestational week at delivery will be the time scale continued pregnancy will be the event and results will be compared with a log-rank test Hazard ratio HR values will be estimated using a Cox proportional hazards model with a formal test of the proportional hazard assumption
The secondary outcome will be analysed by reporting continuous variables as mean and standard deviation for normally distributed variables or median and interquartile range Q1 Q3 for non-normally distributed variables Categorical variables will be presented as the number of events and proportions Student T-test or Mann-Whitney U test will be used for continuous outcomes to compare the differences between groups For categorical outcomes the Chi-squared or Fisher exact test will be used In the case of dichotomous endpoints the relative risk RR and 95 confidence interval CI values will be calculated using the Wald or Adjusted Wald methods for a small proportion Per-protocol analysis will also be conducted if needed
A prespecified subgroup analysis will be performed by quartiles of cervical length which tested for interaction between cervical length and the treatment effect on the primary outcome the major secondary outcome and PTB 28 34 37 weeks
The p-values 005 will be considered to indicate statistical significance Statistical analyses will be performed using the R statistical software
Details of the analysis will be described in a separate statistical analysis plan developed during the study and finalized before the data lock Cost data will be collected and will be reported on a separated paper
Interim analysis will be done after completion of data recruitment of the first 162 participants by an independent Data Safety Monitoring Committee The Data Safety Monitoring Committee will be asked to assess the primary endpoint for effectiveness Also the Data Safety Monitoring Committee will be provided insight into the serious adverse events SAEs that have occurred The interim analysis will be conducted using a two-sided significant test with the Haybittle-Peto spending function and a type I error rate of 5 percent with p 0001 Z alpha 329 being a reason to stop the trial The continuation of the study will depend on the advice of Data Safety Monitoring Committee
After written informed consent women will be randomly assigned in a 11 ratio to receive a cervical cerclage with vaginal progesterone or vaginal progesterone only Randomization will be carried out by entering participant details into HOPE Epi a web portal of HOPE Research Center My Duc Hospital Treatment allocation will be assigned according to a computer-generated randomization list stored in the online system with a permuted random block size of 2 4 or 6 Blinding will not be possible due to the nature of interventions However neonatologists assessing the neonates will be unaware of treatment allocation Apart from randomization participants will be monitored and treated according to local protocol
All women at 16 07 to 24 07 weeks gestation with a singleton pregnancy will undergo cervical length measurement and digital examination at screening routinely Women with a cervical length 25 mm will be eligible for the study Eligible women will further undergo a speculum examination to assess the feasibility of treatment with either cervical cerclage or vaginal progesterone and to exclude premature rupture of the membranes acute vaginitis and cervicitis Only women in whom the clinician assesses both treatments as feasible will be randomized
Women allocated to a combined therapy group will receive the intervention according to local protocol within a week after randomization Briefly cervical cerclage McDonald technique will be performed in the operation theatre From the same day of undergoing cerclage participants will be receiving 200 mg vaginal progesterone purchased from the manufacturer Cyclogest 200mg Actavis United Kingdom once daily at bedtime Participants will be asked to record their drug application in a participant diary sheet
Women allocated to the progesterone-only group will be receiving 200 mg vaginal progesterone purchased from the manufacturer Cyclogest 200mg Actavis United Kingdom once daily at bedtime Participants will be asked to record their drug application in a participant diary sheet
In both groups interventions will be stopped at 37 07 weeks of gestation or at delivery
Primary analysis will be performed on an intention-to-treat basis The primary outcome the time from randomization to delivery will be summarised as median and IQR and compared between the two arms using the Mann-Whitney test A mean ratio with a 95 confidence interval will be calculated to assess the effect of the treatment Kaplan-Meier and Cox proportional hazard analysis will be performed in which the gestational week at delivery will be the time scale continued pregnancy will be the event and results will be compared with a log-rank test Hazard ratio HR values will be estimated using a Cox proportional hazards model with a formal test of the proportional hazard assumption
The secondary outcome will be analysed by reporting continuous variables as mean and standard deviation for normally distributed variables or median and interquartile range Q1 Q3 for non-normally distributed variables Categorical variables will be presented as the number of events and proportions Student T-test or Mann-Whitney U test will be used for continuous outcomes to compare the differences between groups For categorical outcomes the Chi-squared or Fisher exact test will be used In the case of dichotomous endpoints the relative risk RR and 95 confidence interval CI values will be calculated using the Wald or Adjusted Wald methods for a small proportion Per-protocol analysis will also be conducted if needed
A prespecified subgroup analysis will be performed by quartiles of cervical length which tested for interaction between cervical length and the treatment effect on the primary outcome the major secondary outcome and PTB 28 34 37 weeks
The p-values 005 will be considered to indicate statistical significance Statistical analyses will be performed using the R statistical software
Details of the analysis will be described in a separate statistical analysis plan developed during the study and finalized before the data lock Cost data will be collected and will be reported on a separated paper
Interim analysis will be done after completion of data recruitment of the first 162 participants by an independent Data Safety Monitoring Committee The Data Safety Monitoring Committee will be asked to assess the primary endpoint for effectiveness Also the Data Safety Monitoring Committee will be provided insight into the serious adverse events SAEs that have occurred The interim analysis will be conducted using a two-sided significant test with the Haybittle-Peto spending function and a type I error rate of 5 percent with p 0001 Z alpha 329 being a reason to stop the trial The continuation of the study will depend on the advice of Data Safety Monitoring Committee
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None