Clinical trial NCT03362697: Lactobacillus Reuteri for Treatment of Uncomplicated UTI in Pregnant Women
Official title: Randomized Clinical Trial on the Safety and Efficacy of Lactobacillus Reuteri DSM 16666/ATCC 55845 & Lactobacillus Reuteri DSM 17938 for Treatment of Pregnant Women With Asymptomatic Bacteriuria or Uncomplicated Acute Cystitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Urinary Tract Infection in Pregnancy
Lead sponsor: Innovacion y Desarrollo de Estrategias en Salud
Sponsor class: OTHER
Collaborators: name: BioGaia AB
First posted: 2017-12-05
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial, double blind allocation concealment, parallel Assignment
Primary purpose: TREATMENT

Brief summary: Prevalence of uro-genital infections during pregnancy move between 7% to 12% in developed countries, meanwhile in developing countries this figure moved between 14% and until 55%, such is the case of Mexico. Meanwhile use of antibiotics for 3 to 7 days had established as a standard of care, the use of non-antibiotic therapy, such as cranberry powder or probiotics for prevention/treatment of this conditions is scarce. Randomized controlled trial aimed to evaluate the safety and efficacy of probiotic vs. antibiotics to treat pregnant women with uncomplicated cystitis or asymptomatic bacteriuria

Detailed description: Randomized controlled trial, aimed to evaluate the efficacy of Lactobacillus reuteri DSM 16666/ATCC 55845 \& Lactobacillus reuteri DSM 17938 for the treatment of pregnant women with asymptomatic bacteriuria or uncomplicated acute cystitis. As primary outcome we will evaluate the number of cases with clinical (symptoms severity) or bacteriological cure in pregnant women with uncomplicated cystitis or asymptomatic bacteriuria after 7 days treatment with probiotics vs. placebo. As secondary outcome we will evaluate a) rate of recurrence cases in each group; b) time to relapse; c) frequency of pyelonephritis; d) birth weight and head circumference; d) number of cases of preterm babies (less than 36 weeks of gestation); e) frequency of antibiotic as rescue treatment; f) frequency of adverse related events in each arm and g) frequency of preeclampsia. Women on active group will receive a combination of at least 5\*10\^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 \& Lactobacillus reuteri DSM 17938, PAC-A and Zinc. Women in control group will receive o Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) ror patients with positive dipstick.

Eligibility criteria: Inclusion Criteria:

* Healthy women on the second or third trimester of pregnancy with positive urine culture according to the operational definition with or without symptoms
* Age 18 to 40 years
* Verbal and Written Informed Consent for participation in the study

Exclusion Criteria:

* Pathologic pregnancy (different for UTI)
* No supplementation of probiotics 2 weeks before study start or during the study period.
* Antibiotic therapy within last 2 weeks before randomization
* Known allergies towards the ingredients of the experimental product
* Inability to comprehend the study protocol
* Systemic diseases
* Multiple pregnancy

Primary outcomes:
measure: Clinical and/or Bacteriological cure
timeFrame: 14 days
Secondary outcomes:
measure: Recurrence rate
timeFrame: 6 months
measure: Time to relapse
timeFrame: 6 months
measure: Frequency of pyelonephritis
timeFrame: 6 months
measure: Frequency of preterm babies
timeFrame: 6 months
measure: Antibiotic rescue
timeFrame: 6 months
measure: Adverse events
timeFrame: 14 days
Other outcomes:
Locations:
city: Mexico city
country: Mexico
facility: Hospital General Dr. Manuel Gea Gonzalez
state: Tlalpan
Study officials:
References:
citation: Nicolle LE. Asymptomatic bacteriuria: when to screen and when to treat. Infect Dis Clin North Am. 2003 Jun;17(2):367-94. doi: 10.1016/s0891-5520(03)00008-4.
citation: Colgan R, Williams M. Diagnosis and treatment of acute uncomplicated cystitis. Am Fam Physician. 2011 Oct 1;84(7):771-6.
citation: Colgan R, Williams M, Johnson JR. Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician. 2011 Sep 1;84(5):519-26.
citation: Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.
citation: Kazemier BM, Koningstein FN, Schneeberger C, Ott A, Bossuyt PM, de Miranda E, Vogelvang TE, Verhoeven CJ, Langenveld J, Woiski M, Oudijk MA, van der Ven JE, Vlegels MT, Kuiper PN, Feiertag N, Pajkrt E, de Groot CJ, Mol BW, Geerlings SE. Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: a prospective cohort study with an embedded randomised controlled trial. Lancet Infect Dis. 2015 Nov;15(11):1324-33. doi: 10.1016/S1473-3099(15)00070-5. Epub 2015 Aug 5.
citation: Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight. Obstet Gynecol. 1989 Apr;73(4):576-82.
citation: Ho M, Chang YY, Chang WC, Lin HC, Wang MH, Lin WC, Chiu TH. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: A randomized controlled trial. Taiwan J Obstet Gynecol. 2016 Aug;55(4):515-8. doi: 10.1016/j.tjog.2016.06.003.