Efficacy Study of Preconception Treatment of an Asymptomatic Bacterial Infection in an Infertility Population

NCT01322971 | Terminated Results

• 2 other identifiers: SU-03212011-7604IRB Protocol Number 20103
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Bacterial vaginosis (BV) is a common vaginal infection characterized by a pathologic shift in the normal vaginal flora. BV has been associated with a number of poor reproductive outcomes, including infertility, preterm labor and premature rupture of membranes. If BV does disrupt normal embryologic development, then the treatment of BV prior to conception may improve implantation rates and other pregnancy outcomes in the infertile population. This is a prospective, randomized, double-blind, placebo-controlled trial in which infertile women undergoing intrauterine insemination or embryo transfer are screened for BV prior to treatment. Those patients who screen positive for BV will then be randomized into the treatment arm(metronidazole 500mg by mouth twice daily for 7 days) or the control arm (placebo by mouth twice daily for 7 days). The primary outcome, positive pregnancy test rate (i.e. biochemical pregnancy rate), will then be assessed. Secondary outcomes, such as clinical pregnancy rate, miscarriage rate, and live birth rate will also be examined.

Conditions

Vaginosis, Bacterial; Infertility; Miscarriage

Keywords

Bacterial Vaginosis; Infertility; Miscarriage; Metronidazole

Outcome Measures

Primary Outcomes (1)

• Biochemical Pregnancy Rate (Positive Pregnancy Test)

  Biochemical pregnancy rate was defined as number of participants who had a positive pregnancy test

  up to 2 years

Secondary Outcomes (3)

• Pregnancy Rate (Pregnancy Visible on Ultrasound)

  up to 2 years

• Miscarriage Rate (Loss of a Clinically Recognized Pregnancy)

  up to 2 years

• Infectious Morbidity (i.e. Chorioamnionitis, Neonatal Sepsis)

  up to 2 years

Study Arms (2)

Metronidazole

ACTIVE COMPARATOR

Patients randomized to the metronidazole arm will receive metronidazole 500mg orally twice daily for seven days.

Drug: Metronidazole

Placebo

PLACEBO COMPARATOR

Patients randomized to the placebo arm will receive placebo orally twice daily for seven days(control arm

Drug: Placebo

Interventions

Metronidazole DRUG

Metronidazole 500mg orally twice daily for seven days

Metronidazole

Placebo DRUG

Placebo will be administered orally twice daily for seven days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who are actively trying to conceive via intrauterine insemination or in vitro fertilization

You may not qualify if:

• Current use of an oral or vaginal antibiotic.
• History of allergy or adverse reaction to metronidazole.
• Prior enrollment in study (patients returning for repeat cycle may not be re-enrolled).

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Ruth Lathi

Stanford, California, 94305, United States

Location

Related Publications (13)

• American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January 2001). Obstet Gynecol. 2001 Oct;98(4):709-16.

  PMID: 11592272 BACKGROUND

• Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, Heine RP, Nugent RP, Fischer ML, Leveno KJ, Wapner R, Varner M. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 2000 Feb 24;342(8):534-40. doi: 10.1056/NEJM200002243420802.

  PMID: 10684911 BACKGROUND

• Donders GG, Van Bulck B, Caudron J, Londers L, Vereecken A, Spitz B. Relationship of bacterial vaginosis and mycoplasmas to the risk of spontaneous abortion. Am J Obstet Gynecol. 2000 Aug;183(2):431-7. doi: 10.1067/mob.2000.105738.

  PMID: 10942482 BACKGROUND

• Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C, Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 1994 Jan 29;308(6924):295-8. doi: 10.1136/bmj.308.6924.295.

  PMID: 8124116 BACKGROUND

• Hay PE. Bacterial vaginosis and miscarriage. Curr Opin Infect Dis. 2004 Feb;17(1):41-4. doi: 10.1097/00001432-200402000-00008.

  PMID: 15090889 BACKGROUND

• Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, Cotch MF, Edelman R, Pastorek JG 2nd, Rao AV, et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med. 1995 Dec 28;333(26):1737-42. doi: 10.1056/NEJM199512283332604.

  PMID: 7491137 BACKGROUND

• Korn AP, Bolan G, Padian N, Ohm-Smith M, Schachter J, Landers DV. Plasma cell endometritis in women with symptomatic bacterial vaginosis. Obstet Gynecol. 1995 Mar;85(3):387-90. doi: 10.1016/0029-7844(94)00400-8.

  PMID: 7862377 BACKGROUND

• Liversedge NH, Turner A, Horner PJ, Keay SD, Jenkins JM, Hull MG. The influence of bacterial vaginosis on in-vitro fertilization and embryo implantation during assisted reproduction treatment. Hum Reprod. 1999 Sep;14(9):2411-5. doi: 10.1093/humrep/14.9.2411.

  PMID: 10469722 BACKGROUND

• McDonald HM, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000262. doi: 10.1002/14651858.CD000262.pub3.

  PMID: 17253447 BACKGROUND

• Nelson DB, Bellamy S, Nachamkin I, Ness RB, Macones GA, Allen-Taylor L. First trimester bacterial vaginosis, individual microorganism levels, and risk of second trimester pregnancy loss among urban women. Fertil Steril. 2007 Nov;88(5):1396-403. doi: 10.1016/j.fertnstert.2007.01.035. Epub 2007 Apr 16.

  PMID: 17434499 BACKGROUND

• Platz-Christensen JJ, Brandberg A, Wiqvist N. Increased prostaglandin concentrations in the cervical mucus of pregnant women with bacterial vaginosis. Prostaglandins. 1992 Feb;43(2):133-4. doi: 10.1016/0090-6980(92)90082-5.

  PMID: 1542740 BACKGROUND

• Platz-Christensen JJ, Mattsby-Baltzer I, Thomsen P, Wiqvist N. Endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis. Am J Obstet Gynecol. 1993 Nov;169(5):1161-6. doi: 10.1016/0002-9378(93)90274-m.

  PMID: 8238178 BACKGROUND

• Wilson JD, Ralph SG, Rutherford AJ. Rates of bacterial vaginosis in women undergoing in vitro fertilisation for different types of infertility. BJOG. 2002 Jun;109(6):714-7. doi: 10.1111/j.1471-0528.2002.01297.x.

  PMID: 12118653 BACKGROUND

MeSH Terms

Conditions

Vaginosis, Bacterial; Infertility; Abortion, Spontaneous

Interventions

Metronidazole

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Pregnancy Complications

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

151 screened 2 were randomized both refused to take medication not knowing if it were placebo or drug

Results Point of Contact

• Title: Ruth Lathi
• Organization: Stanford University

rlathi@stanford.edu

Study Officials

• Ruth Bunker Lathi

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: March 25, 2011
• Study Start: February 1, 2011
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 20, 2021
• Results First Posted: January 20, 2017

Record last verified: 2021-12

Locations

US (1)