Preterm Birth
Conditions
Keywords
Short cervix, preterm birth, arabin pessary
Brief summary
Placement of a vaginal pessary reduces significantly the rate of spontaneous preterm birth in pregnant women with short cervical length at 18-22 weeks scan.
Detailed description
This trial includes pregnant women undergoing routine ultrasound examination at 18.0 to 22.6 weeks of gestation.
Interventions
DEVICESilicon ring (Arabin Pessary)
Placement of a silicon pessary in the vagina, around the cervix.
Sponsors
Hospital Universitario de Canarias
Hospital Son Llatzer
Fundacion Dexeus
Maternal-Infantil Vall d´Hebron Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Singleton pregnancy * Minimal age of 18 years
Exclusion criteria
* Major fetal abnormalities (requiring surgery or leading to infant death or severe handicap) * SROM at the time of randomization * Cervical cerclage in situ * Active vaginal bleeding * Previous cone biopsy or cerclage * Major uterine structural anomalies * Placenta previa
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous Delivery Before 34 Completed Weeks | Between 24 and 34 weeks | Number of spontaneous preterm births before 34 weeks occurred in each group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chorioamnionitis | participants will be followed for the duration of pregnancy, up to nine months | Number of participants that showed intrauterine infection diagnosed by maternal tachycardia, fever, uterine tenderness, purulent or abnormal cervical discharge, fetal tachycardia. |
| Birthweight Less Than 1500 g | Time of delivery | Number of newborns whose birthweight is less than 1500 grams |
| Birthweight Less Than 2500 g | Time of delivery | Number of newborns whose birthweight is less than 2500 grams |
| Intrauterine Fetal Demise | Pregnancy | The number of fetal deaths in the pessary group was compared to those in the no pessary group |
| Neonatal Death | Between birth and 28 days of age | The number of neonatal deaths in the pessary group was compared to those in the no pessary group |
| Intraventricular Haemorrhage | Between birth and 28 days of age | The number of neonatal intraventricular haemorrhage in the pessary group was compared to those in the no pessary group |
| Respiratory Distress Syndrome | Between birth and 28 days of age | The number of neonatal Respiratory distress syndrome in the pessary group was compared to those in the no pessary group |
| Retinopathy of Prematurity | Between birth and 28 days of age | The number of neonatal retinopathy in the pessary group was compared to those in the no pessary group |
| Necrotising Enterocolitis | Between birth and 28 days of age | The number of neonatal necrotising enterocolitis in the pessary group was compared to those in the no pessary group |
| Treatment for Sepsis | Between birth and 28 days of age | The number of neonatal cases of treatment needed for sepsis in the pessary group was compared to those in the no pessary group |
| Composite Adverse Outcomes | Between birth and 28 days of age | The number of neonatal cases with composite adverse outcomes in the pessary group was compared to those in the no pessary group |
| Use of Antenatal Steroids | participants will be followed for the duration of pregnancy, up to nine months | Number of participants that received betamethasone to reduce morbidity of expected preterm delivery |
| Any Delivery Before 34 Completed Weeks | Between 24 and 34 weeks | Number of all preterm births before 34 weeks occurred in each group. |
| Spontaneous Delivery Before 37 Completed Weeks | Between 24 and 37 weeks | Number of preterm births before 37 weeks occurred in each group. |
| Gestational Age at Delivery | At time of birth | Number of weeks of gestation completed by time of delivery |
| Use of Tocolysis | participants will be followed for the duration of pregnancy, up to nine months | Number of participants required use of tocolytic medication |
| Vaginal Bleeding | participants will be followed for the duration of pregnancy, up to nine months | Number of participants who experienced bleeding from lower genital tract during antepartum period |
| Preterm Premature Rupture of Membranes | participants will be followed for the duration of pregnancy, up to nine months | Number of participants who experienced rupture of membranes as diagnosed by speculum exam showing pooling, ferning, positive nitrazine test, positive amnisure test. |
| Cesarean Delivery | At time of delivery | Number of participants that underwent cesarean delivery |
| Vaginal Discharge | participants will be followed for the duration of pregnancy, up to nine months | Number of participants who experienced an increased vaginal discharge. |
| Pessary Repositioning Without Removal | participants will be followed for the duration of pregnancy, up to nine months | Number of participants who required pessary repositioning without removal. This outcome measure only applied to the Experimental (Pessary Arm) and no data were collected from participants in the No Intervention \_(No Pessary Arm). |
| Pessary Withdrawal | participants will be followed for the duration of pregnancy, up to nine months | Number of participants who experience pessary withdrawal. This outcome measure only applied to the Experimental (Pessary Arm) and no data were collected from participants in the No Intervention \_(No Pessary Arm). |
| Spontaneous Delivery Before 28 Completed Weeks | Between 24 and 28 weeks | Number of preterm births before 28 weeks occurred in each group. |
Countries
Spain
Participant flow
Recruitment details
You are right that our fi rst planned sample size was 2780 patients. However, after the first interim analysis, and in accordance with the advice of our Data Monitoring Committee, the protocol was amended to reach the new and fi nal sample size.
Participants by arm
| Arm | Count |
|---|---|
| Expectant Management Both groups were seen by the clinical team of the trial at each centre every month until delivery. Transabdominal ultrasonography was done for fetal biometries and wellbeing, clinical questionnaire was administered for confi rmation of correct device placement in the pessary group (fi gure 2), vaginal swab was taken for study of bacteriological infection, and transvaginal ultra sonography was done to measure cervical length (fi gure 3) | 190 |
| Placement of Arabin Pessary Since 23 Weeks Until 37 Weeks The pessary was removed during the 37th week of gestation. Indications for pessary removal before this time were active vaginal bleeding, risk of preterm labour with persistent contractions despite tocolysis, or severe patient discomfort. | 190 |
| Total | 380 |
Baseline characteristics
| Characteristic | Expectant Management | Placement of Arabin Pessary Since 23 Weeks Until 37 Weeks | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 190 Participants | 190 Participants | 380 Participants |
| Age, Continuous | 29.6 years STANDARD_DEVIATION 5.4 | 30.3 years STANDARD_DEVIATION 5.1 | 30.1 years STANDARD_DEVIATION 5.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 56 Participants | 58 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 134 Participants | 132 Participants | 266 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Spain | 190 participants | 190 participants | 380 participants |
| Sex: Female, Male Female | 190 Participants | 190 Participants | 380 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 190 | 0 / 190 |
| other Total, other adverse events | 0 / 190 | 0 / 190 |
| serious Total, serious adverse events | 0 / 190 | 0 / 190 |
Outcome results
Primary
Spontaneous Delivery Before 34 Completed Weeks
Number of spontaneous preterm births before 34 weeks occurred in each group.
Time frame: Between 24 and 34 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Spontaneous Delivery Before 34 Completed Weeks | 51 Participants |
| Experimental: Pessary | Spontaneous Delivery Before 34 Completed Weeks | 12 Participants |
Secondary
Any Delivery Before 34 Completed Weeks
Number of all preterm births before 34 weeks occurred in each group.
Time frame: Between 24 and 34 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Any Delivery Before 34 Completed Weeks | 53 Participants |
| Experimental: Pessary | Any Delivery Before 34 Completed Weeks | 14 Participants |
Secondary
Birthweight Less Than 1500 g
Number of newborns whose birthweight is less than 1500 grams
Time frame: Time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Birthweight Less Than 1500 g | 26 Participants |
| Experimental: Pessary | Birthweight Less Than 1500 g | 9 Participants |
Secondary
Birthweight Less Than 2500 g
Number of newborns whose birthweight is less than 2500 grams
Time frame: Time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Birthweight Less Than 2500 g | 56 Participants |
| Experimental: Pessary | Birthweight Less Than 2500 g | 17 Participants |
Secondary
Cesarean Delivery
Number of participants that underwent cesarean delivery
Time frame: At time of delivery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Cesarean Delivery | 40 Participants |
| Experimental: Pessary | Cesarean Delivery | 41 Participants |
Secondary
Chorioamnionitis
Number of participants that showed intrauterine infection diagnosed by maternal tachycardia, fever, uterine tenderness, purulent or abnormal cervical discharge, fetal tachycardia.
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Chorioamnionitis | 6 Participants |
| Experimental: Pessary | Chorioamnionitis | 5 Participants |
Secondary
Composite Adverse Outcomes
The number of neonatal cases with composite adverse outcomes in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Composite Adverse Outcomes | 30 Participants |
| Experimental: Pessary | Composite Adverse Outcomes | 5 Participants |
Secondary
Gestational Age at Delivery
Number of weeks of gestation completed by time of delivery
Time frame: At time of birth
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention: No Pessary | Gestational Age at Delivery | 34.9 weeks | Standard Deviation 4 |
| Experimental: Pessary | Gestational Age at Delivery | 37.7 weeks | Standard Deviation 2 |
Secondary
Intrauterine Fetal Demise
The number of fetal deaths in the pessary group was compared to those in the no pessary group
Time frame: Pregnancy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Intrauterine Fetal Demise | 0 Participants |
| Experimental: Pessary | Intrauterine Fetal Demise | 0 Participants |
Secondary
Intraventricular Haemorrhage
The number of neonatal intraventricular haemorrhage in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Intraventricular Haemorrhage | 2 Participants |
| Experimental: Pessary | Intraventricular Haemorrhage | 0 Participants |
Secondary
Necrotising Enterocolitis
The number of neonatal necrotising enterocolitis in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Necrotising Enterocolitis | 2 Participants |
| Experimental: Pessary | Necrotising Enterocolitis | 0 Participants |
Secondary
Neonatal Death
The number of neonatal deaths in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Neonatal Death | 1 Participants |
| Experimental: Pessary | Neonatal Death | 0 Participants |
Secondary
Pessary Repositioning Without Removal
Number of participants who required pessary repositioning without removal. This outcome measure only applied to the Experimental (Pessary Arm) and no data were collected from participants in the No Intervention \_(No Pessary Arm).
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Pessary Repositioning Without Removal | 0 Participants |
| Experimental: Pessary | Pessary Repositioning Without Removal | 27 Participants |
Secondary
Pessary Withdrawal
Number of participants who experience pessary withdrawal. This outcome measure only applied to the Experimental (Pessary Arm) and no data were collected from participants in the No Intervention \_(No Pessary Arm).
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Pessary Withdrawal | 0 Participants |
| Experimental: Pessary | Pessary Withdrawal | 1 Participants |
Secondary
Preterm Premature Rupture of Membranes
Number of participants who experienced rupture of membranes as diagnosed by speculum exam showing pooling, ferning, positive nitrazine test, positive amnisure test.
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Preterm Premature Rupture of Membranes | 17 Participants |
| Experimental: Pessary | Preterm Premature Rupture of Membranes | 3 Participants |
Secondary
Respiratory Distress Syndrome
The number of neonatal Respiratory distress syndrome in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Respiratory Distress Syndrome | 23 Participants |
| Experimental: Pessary | Respiratory Distress Syndrome | 5 Participants |
Secondary
Retinopathy of Prematurity
The number of neonatal retinopathy in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Retinopathy of Prematurity | 2 Participants |
| Experimental: Pessary | Retinopathy of Prematurity | 0 Participants |
Secondary
Spontaneous Delivery Before 28 Completed Weeks
Number of preterm births before 28 weeks occurred in each group.
Time frame: Between 24 and 28 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Spontaneous Delivery Before 28 Completed Weeks | 16 Participants |
| Experimental: Pessary | Spontaneous Delivery Before 28 Completed Weeks | 4 Participants |
Secondary
Spontaneous Delivery Before 37 Completed Weeks
Number of preterm births before 37 weeks occurred in each group.
Time frame: Between 24 and 37 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Spontaneous Delivery Before 37 Completed Weeks | 113 Participants |
| Experimental: Pessary | Spontaneous Delivery Before 37 Completed Weeks | 41 Participants |
Secondary
Treatment for Sepsis
The number of neonatal cases of treatment needed for sepsis in the pessary group was compared to those in the no pessary group
Time frame: Between birth and 28 days of age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Treatment for Sepsis | 12 Participants |
| Experimental: Pessary | Treatment for Sepsis | 3 Participants |
Secondary
Use of Antenatal Steroids
Number of participants that received betamethasone to reduce morbidity of expected preterm delivery
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Use of Antenatal Steroids | 121 Participants |
| Experimental: Pessary | Use of Antenatal Steroids | 80 Participants |
Secondary
Use of Tocolysis
Number of participants required use of tocolytic medication
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Use of Tocolysis | 101 Participants |
| Experimental: Pessary | Use of Tocolysis | 64 Participants |
Secondary
Vaginal Bleeding
Number of participants who experienced bleeding from lower genital tract during antepartum period
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Vaginal Bleeding | 9 Participants |
| Experimental: Pessary | Vaginal Bleeding | 7 Participants |
Secondary
Vaginal Discharge
Number of participants who experienced an increased vaginal discharge.
Time frame: participants will be followed for the duration of pregnancy, up to nine months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Intervention: No Pessary | Vaginal Discharge | 87 Participants |
| Experimental: Pessary | Vaginal Discharge | 190 Participants |