Magnesium Sulfate Versus Nifedipine for the Acute Tocolysis of Preterm Labor: A Prospective, Randomized Trial

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00185900
• Collaborator: (none)
• Enrollment: 192
• Location: 1
• Arms: 2
• Duration (Months): 99
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

To compare intravenous magnesium sulfate to oral nifedipine for acute tocolysis of preterm labor

Condition or Disease	Intervention/Treatment	Phase
Obstetric Labor, Premature	Drug: Magnesium Sulfate; Drug: Nifedipine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Magnesium Sulfate Versus Nifedipine for the Acute Tocolysis of Preterm Labor: A Prospective, Randomized Trial
• Study Start Date: Apr 1, 1999
• Actual Primary Completion Date: Jul 1, 2005
• Actual Study Completion Date: Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Magnesium Sulfate Preterm labor treatment with Magnesium Sulfate.	Drug: Magnesium Sulfate; Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.
Active Comparator: Nifedipine Preterm labor treatment with Nifedipine.	Drug: Nifedipine; Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Prevention of Preterm Delivery for 48 Hours With Attainment of Uterine Quiescence [48 hours after administration of study medication.]

   Uterine quiescence defined by 12 hours of six or fewer contractions per hour and no further cervical change within 48 hours of tocolytic initiation.

Secondary Outcome Measures

1. Time to Uterine Quiescence [Until delivery, up to 42 weeks of gestation]

   Uterine quiescence was defined by 12 hours of six of fewer contractions per hour and no further cervical change.

2. Gestational Age at Delivery [Until delivery, up to 42 weeks of gestation]

   Presented as weeks

3. Neonatal Birth Weight [Until delivery, up to 42 weeks of gestation]

   Presented as grams

4. Serious Maternal Adverse Effect [From study enrollment until discharge from delivery hospital, up to 30 days after delivery.]

   A composite of any of the following: chest pain, pulmonary edema, shortness of breath or hypotension.

5. Composite Neonatal Morbidity [From delivery until discharge from the hospital, up to 30 days of age]

   Defined as any of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis or fetal/neonatal death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria::- Uterine contractions and cervical change or ruptured membranes in a preterm gestation Exclusion Criteria:- placental abruption, fetal distress, placenta previa, maternal medical contraindication to tocolysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Yasser Yehia El-Sayed, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Obstet Gynecol. 2007 Jul;110(1):61-7.

Publications

None provided.

• Responsible Party: Yasser Yehia El-Sayed, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT00185900
• Other Study ID Numbers: 76145
• First Posted: Sep 16, 2005
• Last Update Posted: Nov 19, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Obstetric Labor, Premature; Magnesium Sulfate; Nifedipine

Study Results

Participant Flow

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Period Title: Overall Study
STARTED	92	100
COMPLETED	92	100
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Magnesium Sulfate	Nifedipine	Total
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.	Total of all reporting groups
Overall Participants	92	100	192
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.6 (6.8)	26.3 (6.3)	26.5 (6.6)
Sex: Female, Male (Count of Participants)
Female	92 100%	100 100%	192 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	92 100%	100 100%	192 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Prevention of Preterm Delivery for 48 Hours With Attainment of Uterine Quiescence
Description	Uterine quiescence defined by 12 hours of six or fewer contractions per hour and no further cervical change within 48 hours of tocolytic initiation.
Time Frame	48 hours after administration of study medication.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	92	100
Count of Participants [Participants]	80 87%	72 72%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Magnesium Sulfate, Nifedipine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Time to Uterine Quiescence
Description	Uterine quiescence was defined by 12 hours of six of fewer contractions per hour and no further cervical change.
Time Frame	Until delivery, up to 42 weeks of gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	92	100
Mean (Standard Deviation) [hours]	8.4 (6.5)	6.1 (6.3)

3. Secondary Outcome

Title	Gestational Age at Delivery
Description	Presented as weeks
Time Frame	Until delivery, up to 42 weeks of gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	92	100
Mean (Standard Deviation) [weeks]	35.8 (3.4)	36.0 (3.1)

4. Secondary Outcome

Title	Neonatal Birth Weight
Description	Presented as grams
Time Frame	Until delivery, up to 42 weeks of gestation

Outcome Measure Data

Analysis Population Description

Data included twins, so the group totals are greater than seen in the Overall Number of Participants Analyzed

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	106	110
Mean (Standard Deviation) [grams]	2550 (802)	2650 (698)

5. Secondary Outcome

Title	Serious Maternal Adverse Effect
Description	A composite of any of the following: chest pain, pulmonary edema, shortness of breath or hypotension.
Time Frame	From study enrollment until discharge from delivery hospital, up to 30 days after delivery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	92	100
Count of Participants [Participants]	20 21.7%	10 10%

6. Secondary Outcome

Title	Composite Neonatal Morbidity
Description	Defined as any of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, sepsis or fetal/neonatal death.
Time Frame	From delivery until discharge from the hospital, up to 30 days of age

Outcome Measure Data

Analysis Population Description

Data included twins, so the group totals are greater than seen in the Overall Number of Participants Analyzed.

Arm/Group Title	Magnesium Sulfate	Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.	Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
Measure Participants	106	110
Count of Participants [Participants]	27 29.3%	22 22%

Adverse Events

Time Frame	From study enrollment until discharge from the delivery hospital, up to 30 days after delivery.
Adverse Event Reporting Description	Adverse events were assessed by patient interview from a list of adverse effects and chart review.
Arm/Group Title	Magnesium Sulfate		Nifedipine
Arm/Group Description	Preterm labor treatment with Magnesium Sulfate. Magnesium Sulfate: Preterm labor treatment with Magnesium Sulfate 4 gram bolus followed by 2 gm per hour infusion. 2 Gm bolus as needed and/or rate increase up to 4gm per hour were allowed at the discretion of the treating physician.		Preterm labor treatment with Nifedipine. Nifedipine: Preterm labor treatment with Nifedipine 10 mg. sublingually every 20 minutes for three doses, followed by 20 mg. orally every 4 or 6 hours.
All Cause Mortality
	Magnesium Sulfate		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/100 (0%)
Serious Adverse Events
	Magnesium Sulfate		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/92 (27.2%)		12/100 (12%)
Cardiac disorders
Chest pain	7/92 (7.6%)		4/100 (4%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath	13/92 (14.1%)		5/100 (5%)
Pulmonary edema	3/92 (3.3%)		0/100 (0%)
Vascular disorders
Hypotension	2/92 (2.2%)		3/100 (3%)
Other (Not Including Serious) Adverse Events
	Magnesium Sulfate		Nifedipine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/92 (31.5%)		22/100 (22%)
Cardiac disorders
Palpitations	1/92 (1.1%)		0/100 (0%)
Eye disorders
Blurry Vision	12/92 (13%)		0/100 (0%)
Double vision	3/92 (3.3%)		0/100 (0%)
Gastrointestinal disorders
Nausea	29/92 (31.5%)		6/100 (6%)
Vomiting	24/92 (26.1%)		5/100 (5%)
Heartburn	6/92 (6.5%)		6/100 (6%)
Nervous system disorders
Lethargy	27/92 (29.3%)		3/100 (3%)
Dizziness	16/92 (17.4%)		3/100 (3%)
Headache	11/92 (12%)		22/100 (22%)
Skin and subcutaneous tissue disorders
Flushing	20/92 (21.7%)		1/100 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.