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Study halted due to slow recruitment
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Tocolytic agents are used for the treatment of preterm labor. It is unclear whether combination treatments of two tocolytic agents are more effective in stopping preterm labor compared to one. Therefore, the investigators propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor
The investigators current treatment for preterm labor has not been shown to be effective in prolonging pregnancy sufficiently to improve neonatal outcomes and other treatment strategies are needed. Multiple examples demonstrate that multi-agent treatments are routine clinical practice in other fields of medicine including chemotherapeutics for cancer, multi-therapeutics for myocardial infarction and broad spectrum antibiotics for pneumonia. At this time, it is unclear if a combination of tocolytic medications for preterm labor is more advantageous for women. If pregnancy is prolonged with combined tocolytic therapy, this could directly influence the treatment of preterm labor and potentially improve neonatal outcomes. There currently are no trials of combination regimens using widely used tocolytic agents, such as nifedipine and indomethacin. Thus, we propose a comparative effective trial of nifedipine plus indomethacin vs. nifedipine alone for the treatment of preterm labor
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nifedipine | Active Comparator | Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours. |
|
| Nifedipine plus Indomethacin | Active Comparator | Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours for a total of 48 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nifedipine | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation | 48 hours after administration of tocolytic agent |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation | 7 days after administration of tocolytic agent | |
| Number of Days From First Dose of Tocolytic Agent to Delivery | Length of time from tocolytic initiation to the time of delivery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maria Hutchinson, M.S. | The University of Texas Health Science Center, Houston | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Hermann Hospital Texas Medical Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35947046 | Derived | Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, Coomarasamy A, Tobias A, Chou D, Oladapo OT, Price MJ, Morris K, Gallos ID. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022 Aug 10;8(8):CD014978. doi: 10.1002/14651858.CD014978.pub2. |
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The numbers listed in the Participant Flow section correspond to maternal participants.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nifedipine | Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours. |
| FG001 | Nifedipine Plus Indomethacin | Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline characteristics are reported for all who completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Nifedipine | Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours. |
| BG001 | Nifedipine Plus Indomethacin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Maternal Participants Who Achieve 48 Hours of Pregnancy Prolongation | Data for this outcome measure were not collected for 4 in the Nifedipine arm. | Posted | Count of Participants | Participants | 48 hours after administration of tocolytic agent |
|
Maternal participants: from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) Neonates: from birth until hospital discharge or day 120 of life (whichever occurs first)
Adverse Events are reported for 20 maternal participants and 26 neonates in the Nifedipine arm (6 mothers in the Nifedipine arm had twins) and are reported for 22 maternal participants and 23 neonates in the Nifedipine Plus Indomethacin arm (1 mother in the Nifedipine Plus Indomethacin arm had twins). The 2 deaths were neonatal deaths (there were no maternal deaths).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nifedipine | Participants will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death (neonatal) | General disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache (maternal) | General disorders | Systematic Assessment |
Small sample size
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jerrie S. Refuerzo, MD | The University of Texas Health Science Center at Houston | (713) 500-6416 | Jerrie.S.Refuerzo@uth.tmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 2, 2018 | Oct 25, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| ID | Term |
|---|---|
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D009543 | Nifedipine |
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Indomethacin |
| Drug |
|
| from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
| Neonatal Birthweight | at the time of birth |
| Neonatal Sex | at the time of birth |
| Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU) | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Neonatal Length of Stay in NICU | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Neonatal Length of Hospital Stay | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonatal Deaths | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates With Necrotizing Enterocolitis | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates With Culture-positive Sepsis | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates With Seizures | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates Who Needed Mechanical Ventilation | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Neonatal Duration of Ventilator Use | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP) | from birth until hospital discharge or day 120 of life (whichever occurs first) |
| Number of Maternal Participants Who Delivered by Cesarean Delivery | at the the time of birth |
| Number of Maternal Participants Who Had Clinical Chorioamnionitis | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
| Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM) | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
| Number of Maternal Participants Who Had Preeclampsia | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
| Number of Maternal Participants Who Needed Blood Transfusion | from time of birth to time of discharge from hospital (about 2-3 days) |
| Number of Maternal Participants With Headache | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Nausea | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Vomiting | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Acid Reflux | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Hypotension | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Tachycardia | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
| Number of Maternal Participants With Syncope | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Secondary | Number of Maternal Participants Who Achieve 7 Days of Pregnancy Prolongation | Data for this outcome measure were not collected for 4 in the Nifedipine arm. | Posted | Count of Participants | Participants | 7 days after administration of tocolytic agent |
|
|
|
| Secondary | Number of Days From First Dose of Tocolytic Agent to Delivery | Length of time from tocolytic initiation to the time of delivery | Data for this outcome measure were not collected for 4 in the Nifedipine arm. | Posted | Median | Inter-Quartile Range | days | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
|
|
|
| Secondary | Neonatal Birthweight | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Median | Inter-Quartile Range | grams | at the time of birth |
|
|
|
| Secondary | Neonatal Sex | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | at the time of birth |
|
|
|
| Secondary | Number of Neonates Who Were Admitted to the Neonatal Intensive Care Unit (NICU) | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Neonatal Length of Stay in NICU | Data for this outcome measure were not collected for 10 neonates in the Nifedipine arm and 10 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Median | Inter-Quartile Range | days | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Neonatal Length of Hospital Stay | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 1 neonate in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Median | Inter-Quartile Range | days | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonatal Deaths | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates With Intraventricular Hemorrhage Diagnosed Using Cranial Ultrasonography | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates With Necrotizing Enterocolitis | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates With Culture-positive Sepsis | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates With Seizures | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates Who Needed Mechanical Ventilation | Data for this outcome measure were not collected for 4 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Neonatal Duration of Ventilator Use | Data for this outcome measure were not collected for 22 neonates in the Nifedipine arm and 20 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Median | Inter-Quartile Range | hours | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Neonates Who Received Continuous Positive Airway Pressure (CPAP) | Data for this outcome measure were not collected for 5 neonates in the Nifedipine arm and 2 neonates in the Nifedipine plus Indomethacin arm. (There are more neonates than maternal participants because 6 mothers in the Nifedipine arm had twins and 1 mother in the Nifedipine plus Indomethacin arm had twins.) | Posted | Count of Participants | Participants | from birth until hospital discharge or day 120 of life (whichever occurs first) |
|
|
|
| Secondary | Number of Maternal Participants Who Delivered by Cesarean Delivery | Data for this outcome measure were not collected for 4 in the Nifedipine arm. | Posted | Count of Participants | Participants | at the the time of birth |
|
|
|
| Secondary | Number of Maternal Participants Who Had Clinical Chorioamnionitis | Data for this outcome measure were not collected for 4 in the Nifedipine arm and 1 in the Nifedipine plus Indomethacin arm. | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants Who Had Preterm Premature Rupture of Membranes (PPROM) | Data for this outcome measure were not collected for 4 in the Nifedipine arm and 1 in the Nifedipine plus Indomethacin arm. | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants Who Had Preeclampsia | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of delivery (from about 1 day to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants Who Needed Blood Transfusion | Posted | Count of Participants | Participants | from time of birth to time of discharge from hospital (about 2-3 days) |
|
|
|
| Secondary | Number of Maternal Participants With Headache | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Nausea | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Vomiting | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Acid Reflux | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Hypotension | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Tachycardia | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| Secondary | Number of Maternal Participants With Syncope | Posted | Count of Participants | Participants | from time of tocolytic initiation to the time of hospital discharge (from about 2 days to about 2 months) |
|
|
|
| 1 |
| 46 |
| 24 |
| 46 |
| 4 |
| 46 |
| EG001 | Nifedipine Plus Indomethacin | Participants will receive will receive nifedipine 10 mg orally every 20 minutes for 3 doses, then nifedipine 10 mg every 6 hours, for a total of 48 hours, as well as indomethacin 100 mg orally, then indomethacin 50 mg orally every 6 hours, for a total of 48 hours. | 1 | 45 | 38 | 45 | 4 | 45 |
| Admission to NICU (neonatal) | General disorders | Systematic Assessment |
|
| Intraventricular Hemorrhage (neonatal) | Vascular disorders | Systematic Assessment |
|
| Necrotizing Enterocolitis (neonatal) | Infections and infestations | Systematic Assessment |
|
| Culture-Positive Sepsis (neonatal) | Infections and infestations | Systematic Assessment |
|
| Seizures (neonatal) | Nervous system disorders | Systematic Assessment |
|
| Received Mechanical Ventilation (neonatal) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Received Continuous Positive Airway Pressure (CPAP) (neonatal) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory distress syndrome (RDS) (neonatal) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Retinopathy of prematurity (neonatal) | Eye disorders | Systematic Assessment |
|
| Received Blood Transfusion (maternal) | General disorders | Systematic Assessment |
|
| Nausea (maternal) | General disorders | Systematic Assessment |
|
| Acid Reflux (maternal) | Gastrointestinal disorders | Systematic Assessment |
|
| Hypotension (maternal) | Vascular disorders | Systematic Assessment |
|
| Tachycardia (maternal) | Cardiac disorders | Systematic Assessment |
|
| Clinical Chorioamnionitis (maternal) | Infections and infestations | Systematic Assessment |
|
| Preterm Premature Rupture of Membranes (PPROM) (maternal) | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Preeclampsia (maternal) | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |