Management of Acute Preterm Labor: Nifedipen Alone or Combined With Cildenafil Citrate

Study Overview
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Brief Summary
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The aim of this study is to assess whether or not the emergency tocolytic effect of combined nifedipine and sildenafil citrate will have a superior effect over nifedipine alone in terms of inhibiting eminent preterm labor and improving perinatal outcomes.

Detailed Description
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Women will be randomly assigned into two study groups using a computerized random number table generator in order to get the trial sequence which will be hidden in sealed numbered opaque envelopes. Each envelope contains a single element (assignment) of the trial sequence. The statistician generated the random allocation sequence, and the investigators enrolled the participants. Each patient will undergo an ultrasound examination prior to randomization to confirm GA, rule out major fetal anomalies and to determine cervical measurements. Dexamethasone in a total dose of 24 mg will be administered to all patients if not given in a previous admission. Eligible women are then randomly assigned into two study groups: Group I: (combined nifedipine and sildenafil citrate) The protocol for nifedipen in our units consists of 20 mg orally stat, followed by 10 mg orally every 6-8 hours, at the same time sildenafil citrate will be administered vaginally in a dose of 25mg at 8 hourly intervals and both medications will be continued for 48-72 hours as indicated. Group II: (nifedipine alone) will receive therapy by nifedipine alone in the same regimen and duration described before. During therapy, maternal (pulse rate, blood pressure, uterine contractions), as well as fetal (heart rate) monitoring will be performed every 15-30 minutes during the first 4 hours following the start of therapy then every 2 hours during the rest of treatment period. Patients whose contractions will stop after 48-72 hours will be observed for additional 24 hours to detect if contractions appear again so that if they remain stable, then they can be discharged and asked to come for follow-up after 1 week. As we stated in a previous work (13) that vaginal progesterone was effective for preventing recurrent PTL, thus all discharged patients will be advised to continue on progesterone till completed 36 weeks' gestation. In addition to progesterone treatment, all patients will be instructed to undergo periods of bed rest and, also they will be educated about the symptoms of PTL. The provided antenatal care will be at 2-weekly intervals till delivery. At any time if preterm contractions appeared re-admission with repeated treatment using the same drug will be used. At delivery, all data regarding the timing of labor onset, along with maternal and neonatal complications, will be documented.

Official Title
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Combined Nifedipine and Sildenafil Citrate Versus Nifedipine Alone in Acute Tocolysis of Preterm Labor: A Randomized Clinical Trial

Conditions
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Labor Preterm Requiring Hospitalization

Intervention / Treatment
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* Drug: nifedipen
* Drug: Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant patients presented in outpatient clinic, admitted through emergency room or referred from any other hospitals will be the candidates for the study if they are of any age, any parity, carrying a singleton pregnancy, at a gestational age (GA) between 24 and 34 weeks, and whether or not they had a previous history of PTL. Exclusion Criteria: The presence of major fetal anomaly, intrauterine fetal death, advanced cervical dilatation (>4cm), membranes bulging into the vagina in asymptomatic women, history of ruptured membranes, major antepartum hemorrhage, major chronic medical disorder (such as chronic hypertension, chronic renal disease, and pre-gestational diabetes mellitus as these conditions would increase the risk of PTL and potentially confound the primary study outcome), twins or higher order multiple pregnancy, any other condition in which continuation of the pregnancy can harm the mother or fetus and any contraindication for nifedipin and/or nicorandil therapy.
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nifedipen and sildenafil<br>The protocol for nifedipen in our units consists of 20 mg orally stat, followed by 10 mg orally every 6-8 hours, at the same time sildenafil citrate will be administered vaginally in a dose of 25mg at 8 hourly intervals and both medications will be continued for 48-72 hours as indicated. | Drug: nifedipen<br>* The protocol for nifedipen in our units consists of 20 mg orally stat, followed by 10 mg orally every 6-8 hours for 48 to 72 hours as needed<br>* Other names: inhibiting acute preterm labor;Drug: Sildenafil<br>* sildenafil citrate will be administered vaginally in a dose of 25mg at 8 hourly intervals and both medications will be continued for 48-72 hours as indicated.<br>* Other names: inhibiting acute preterm labor;|
| Active Comparator: nifedipen only<br>nifedipine alone in the same regimen and duration described before. | Drug: nifedipen<br>* The protocol for nifedipen in our units consists of 20 mg orally stat, followed by 10 mg orally every 6-8 hours for 48 to 72 hours as needed<br>* Other names: inhibiting acute preterm labor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of women remaining undelivered during the whole period of hospitalization. Treatment failure is considered in participants who delivered during this period, or those who need repeated treatment course. |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| readmission after discharge |  | 9 months | 
| time (days) till delivery |  | 9 months | 
| maternal outcomes (gestational age at delivery, mode of delivery, any complications during delivery) |  | 9 months | 
| neonatal outcomes (weight, Apgar score, admission to neonatal intensive care unit |  | 9 months |