A Randomized Controlled Trial of Three Antibiotic Regimens for First Trimester Abortions

• Sponsor: Medstar Health Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02756403
• Collaborator: Society of Family Planning (Other)
• Enrollment: 181
• Locations: 2
• Arms: 4
• Duration (Months): 16
• Patients Per Site: 90.5
• Patients Per Site Per Month: 5.7

Study Details

Study Description

Brief Summary

This study, a double blinded randomized controlled trial, is being done to compare side effects of commonly used antibiotic regimens prior to same day abortion procedures.

In total, 180 pregnant women in their first trimester of pregnancy (5 0/6-13 6/7 weeks gestation) will be randomized to receive one of the three commonly used antibiotics (azithromycin, doxycycline, metronidazole) for same day abortion procedures or placebo prior to their abortion procedure. Approximately, 30-60 mins after study drug administration, the procedure will be performed.

A sub-study will be completed on 40 women who consent to endometrial sampling and to have their blood drawn.

Condition or Disease	Intervention/Treatment	Phase
First Trimester Abortion	Drug: Azithromycin; Drug: Doxycycline; Drug: Metronidazole; Drug: Placebo	N/A

Detailed Description

Main Study:

Women will be randomized to receive single oral doses of azithromycin 500 mg, doxycycline 200 mg, metronidazole 500 mg, or placebo. Computer-generated randomization will be used to assign participants to one of the four treatment arms. Women receiving placebo will receive antibiotic prophylaxis after completion of the study.

Both the participants and the investigators will be blinded as to the treatment group. This will be accomplished by placing the study medication inside opaque gelatin capsules. We will randomize participants by assigning them to the next of the sequentially numbered sealed opaque study packets, containing the gelatin capsules with study medication inside. A second envelope will be opened after completion of all study procedure and will only say if the participant received placebo, so that additional antibiotics can be given.

Participants will swallow the appropriate medication approximately 30-60 minutes prior to the surgical abortion (15-90 minutes range is acceptable). Study population will be all eligible patients undergoing surgical abortion in the first trimester at Washington Hospital Center and Planned Parenthood Metropolitan Washington. We will assess pain and side effects via written questionnaire at three different time points throughout the day, once at time of consent, before and after the procedure. Patients will be contacted within 1-2 weeks for follow-up and again pain and side effects will be assessed, as well.

Sub-study:

Forty (n=40) women will be recruited to undergo immediate post-procedure endometrial sampling. Sub-study patients will have a blood sample collected via venipuncture before leaving the procedure room, as well. No testing will be performed for participants receiving placebo.

The primary objective is to determine if the side effects associated with individual medications are more similar to placebo than the others.

The sub-study aims to explore our ability to identify bacteria within the uterine cavity. The objective is to assess the feasibility of identifying bacteria within the uterus after abortion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 181 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized Controlled Trial of Three Prophylactic Antibiotic Regimens for First Trimester Surgical Abortion
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Azithromycin 500 mg of Azithromycin	Drug: Azithromycin; 500 mg
Active Comparator: Doxycycline 200 mg of Doxycycline	Drug: Doxycycline; 200 mg
Active Comparator: Metronidazole 500 mg of Metronidazole	Drug: Metronidazole; 500 mg
Placebo Comparator: Placebo Inactive Ingredient	Drug: Placebo; Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.

Outcome Measures

Primary Outcome Measures

1. Nausea Scale [1 Day]

   Nausea symptom was collected at different time points via surveys (None, Mild, Moderate, Severe)

2. Emesis Severity [1 Day]

   Emesis severity assessment collected at different time points (None, Mild, Moderate, Severe)

Secondary Outcome Measures

1. Pain Scale [Day 1]

   Pain symptoms will be collected at different time points via surveys (None, Mild, Moderate, Severe)

2. Serum Antibiotic Levels [3 hours]

   Serum antibiotic levels drawn at time of endometrial sampling in subset of patients

3. Endometrial Growth [3 Days]

   Endometrial Growth on non-selective, Staph Selective, Strep Selective, and Gram negative selective Agar

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women in good general health.

• English speaking.

• Age 18 or over.

• Seeking non-urgent surgical termination of pregnancy.

• Gestational age of 5 0/7 to 13 6/7 weeks, confirmed by sonogram.

Exclusion Criteria:

• Less than 18 years of age.

• Early pregnancy failure or fetal demise.

• Poor general health that would prevent one from tolerating the medication or surgical procedure.

• Intolerance, allergy, or contraindication to any of the study medications.

• Inability to tolerate oral intake due to current nausea or vomiting.

• Diagnosis of hyperemesis gravidarum with current pregnancy.

• Need of an urgent surgical abortion.

• Gestational age outside of 5-13 6/7 weeks by sonogram.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
2	Planned Parenthood Metropolitan Washington	Silver Spring	Maryland	United States	20910

Sponsors and Collaborators

• Medstar Health Research Institute
• Society of Family Planning

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 26, 2015

More Information

Publications

None provided.

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT02756403
• Other Study ID Numbers: 2015-159
• First Posted: Apr 29, 2016
• Last Update Posted: Feb 11, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Azithromycin; Metronidazole; Doxycycline

Study Results

Participant Flow

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.
Period Title: Overall Study
STARTED	46	45	43	47
COMPLETED	46	42	41	45
NOT COMPLETED	0	3	2	2

Baseline Characteristics

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo	Total
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.	Total of all reporting groups
Overall Participants	46	42	41	45	174
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.1 (5.0)	26.2 (6.4)	26.5 (5.5)	28.6 (6.1)	26.6 (5.9)
Sex: Female, Male (Count of Participants)
Female	46 100%	42 100%	41 100%	45 100%	174 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 4.3%	0 0%	1 2.4%	2 4.4%	5 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	29 63%	31 73.8%	27 65.9%	34 75.6%	121 69.5%
White	7 15.2%	6 14.3%	7 17.1%	4 8.9%	24 13.8%
More than one race	7 15.2%	4 9.5%	4 9.8%	5 11.1%	20 11.5%
Unknown or Not Reported	1 2.2%	1 2.4%	2 4.9%	0 0%	4 2.3%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.8 (6.2)	27.0 (7.3)	29.5 (8.5)	29.0 (7.0)	28.3 (7.3)
Education (Count of Participants)
Less than High School	4 8.7%	0 0%	3 7.3%	0 0%	7 4%
HS Grad or Equivalent	17 37%	16 38.1%	13 31.7%	16 35.6%	62 35.6%
Some College	14 30.4%	18 42.9%	20 48.8%	17 37.8%	69 39.7%
College Grad	9 19.6%	5 11.9%	4 9.8%	10 22.2%	28 16.1%
Graduate School	2 4.3%	3 7.1%	1 2.4%	2 4.4%	8 4.6%
Parous (Count of Participants)
Nulliparous	21 45.7%	17 40.5%	10 24.4%	17 37.8%	65 37.4%
Parous	25 54.3%	25 59.5%	31 75.6%	28 62.2%	109 62.6%
Marital Status (Count of Participants)
Single	36 78.3%	31 73.8%	34 82.9%	31 68.9%	132 75.9%
Married	4 8.7%	9 21.4%	3 7.3%	5 11.1%	21 12.1%
Divorced	0 0%	1 2.4%	1 2.4%	3 6.7%	5 2.9%
Separated	0 0%	0 0%	0 0%	2 4.4%	2 1.1%
Cohabitating	6 13%	1 2.4%	3 7.3%	4 8.9%	14 8%
Work Status (participants) [Number]
Full Time Work	20 43.5%	19 45.2%	16 39%	23 51.1%	78 44.8%
Part Time Work	8 17.4%	6 14.3%	9 22%	10 22.2%	33 19%
Full Time Student	4 8.7%	5 11.9%	4 9.8%	4 8.9%	17 9.8%
Unemployed	14 30.4%	13 31%	11 26.8%	6 13.3%	44 25.3%
Homemaker	0 0%	1 2.4%	1 2.4%	1 2.2%	3 1.7%
Other	0 0%	0 0%	0 0%	1 2.2%	1 0.6%
Prior Abortion (Count of Participants)
Yes	21 45.7%	21 50%	26 63.4%	34 75.6%	102 58.6%
No	25 54.3%	21 50%	15 36.6%	11 24.4%	72 41.4%
Gestational age (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	60.9 (16.8)	63.9 (17.1)	65 (12.2)	67.5 (15.8)	64.3 (15.7)

Outcome Measures

1. Primary Outcome

Title	Nausea Scale
Description	Nausea symptom was collected at different time points via surveys (None, Mild, Moderate, Severe)
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.
Measure Participants	46	42	41	45
None	8 17.4%	9 21.4%	6 14.6%	6 13.3%
Mild	18 39.1%	15 35.7%	10 24.4%	14 31.1%
Moderate	13 28.3%	11 26.2%	20 48.8%	16 35.6%
Severe	7 15.2%	7 16.7%	5 12.2%	9 20%
None	34 73.9%	36 85.7%	36 87.8%	39 86.7%
Mild	8 17.4%	4 9.5%	5 12.2%	5 11.1%
Moderate	2 4.3%	2 4.8%	0 0%	0 0%
Severe	2 4.3%	0 0%	0 0%	1 2.2%
None	35 76.1%	28 66.7%	34 82.9%	37 82.2%
Mild	7 15.2%	5 11.9%	6 14.6%	8 17.8%
Moderate	4 8.7%	6 14.3%	1 2.4%	0 0%
Severe	0 0%	3 7.1%	0 0%	0 0%

2. Primary Outcome

Title	Emesis Severity
Description	Emesis severity assessment collected at different time points (None, Mild, Moderate, Severe)
Time Frame	1 Day

Outcome Measure Data

Analysis Population Description

4 Subjects failed to complete the entire post-procedure survey: 1 Azithromycin group, 2 in Metronidazole group, 1 in Placebo group

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.
Measure Participants	46	42	41	45
None	20 43.5%	24 57.1%	13 31.7%	17 37.8%
Mild	12 26.1%	8 19%	16 39%	15 33.3%
Moderate	6 13%	6 14.3%	11 26.8%	8 17.8%
Severe	8 17.4%	4 9.5%	1 2.4%	5 11.1%
None	43 93.5%	42 100%	41 100%	44 97.8%
Mild	1 2.2%	0 0%	0 0%	1 2.2%
Moderate	2 4.3%	0 0%	0 0%	0 0%
Severe	0 0%	0 0%	0 0%	0 0%
None	42 91.3%	35 83.3%	39 95.1%	44 97.8%
Mild	2 4.3%	1 2.4%	0 0%	0 0%
Moderate	1 2.2%	5 11.9%	0 0%	0 0%
Severe	0 0%	1 2.4%	0 0%	0 0%

3. Secondary Outcome

Title	Pain Scale
Description	Pain symptoms will be collected at different time points via surveys (None, Mild, Moderate, Severe)
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

4 patients had incomplete post-procedure surveys: 1 in Azithromycin group, 2 in Metronidazole group, 1 in Placebo group

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.
Measure Participants	46	42	41	45
None	20 43.5%	17 40.5%	16 39%	13 28.9%
Mild	18 39.1%	14 33.3%	16 39%	18 40%
Moderate	6 13%	8 19%	6 14.6%	11 24.4%
Severe	2 4.3%	3 7.1%	3 7.3%	3 6.7%
None	35 76.1%	38 90.5%	35 85.4%	39 86.7%
Mild	9 19.6%	4 9.5%	6 14.6%	5 11.1%
Moderate	1 2.2%	0 0%	0 0%	1 2.2%
Severe	1 2.2%	0 0%	0 0%	0 0%
None	18 39.1%	16 38.1%	9 22%	15 33.3%
Mild	18 39.1%	17 40.5%	17 41.5%	16 35.6%
Moderate	6 13%	7 16.7%	12 29.3%	11 24.4%
Severe	3 6.5%	2 4.8%	1 2.4%	2 4.4%

4. Secondary Outcome

Title	Serum Antibiotic Levels
Description	Serum antibiotic levels drawn at time of endometrial sampling in subset of patients
Time Frame	3 hours

Outcome Measure Data

Analysis Population Description

Subset of patients who had serum antibiotic levels drawn

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg
Measure Participants	5	6	8
Mean (Standard Deviation) [mcg/mL]	0.41 (0.22)	1.1 (0.8)	8.2 (3.8)

5. Secondary Outcome

Title	Endometrial Growth
Description	Endometrial Growth on non-selective, Staph Selective, Strep Selective, and Gram negative selective Agar
Time Frame	3 Days

Outcome Measure Data

Analysis Population Description

Subset of patients with endometrial swab cultured

Arm/Group Title	Azithromycin	Doxycycline	Metronidazole	Placebo
Arm/Group Description	500 mg of Azithromycin Azithromycin: 500 mg	200 mg of Doxycycline Doxycycline: 200 mg	500 mg of Metronidazole Metronidazole: 500 mg	Inactive Ingredient Placebo: Placebo pills will be given before the uterine aspiration. Antibiotics will be given after the uterine aspiration.
Measure Participants	7	11	11	4
No Growth	4 8.7%	7 16.7%	8 19.5%	1 2.2%
Trypic Soy Non-Selective Agar	3 6.5%	4 9.5%	3 7.3%	2 4.4%
Mannitol Salt Agar (Staph selective)	1 2.2%	2 4.8%	0 0%	1 2.2%
Streptococcus Agar (Strep selective)	1 2.2%	1 2.4%	1 2.4%	3 6.7%
MacConkey Agar (gram neg selective)	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	One week
Adverse Event Reporting Description	Patients involved in study were called on telephone at one week to assess for any adverse events.
Arm/Group Title	Metronidazole		Azithromycin		Doxycycline		Placebo
Arm/Group Description	Patients receivingMetronidazole for preprocedure antibiotic		Patients receiving Azithromycin for preprocedure antibiotic		Patients receiving Doxycycline for preprocedure antibiotic		Patients receiving Placebo preprocedure
All Cause Mortality
	Metronidazole		Azithromycin		Doxycycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/46 (0%)		0/42 (0%)		0/45 (0%)
Serious Adverse Events
	Metronidazole		Azithromycin		Doxycycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		0/46 (0%)		0/42 (0%)		0/45 (0%)
Pregnancy, puerperium and perinatal conditions
Inpatient Hospitalization	1/41 (2.4%)	1	0/46 (0%)	0	0/42 (0%)	0	0/45 (0%)	0
Other (Not Including Serious) Adverse Events
	Metronidazole		Azithromycin		Doxycycline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/46 (0%)		0/42 (0%)		0/45 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.