Lactobacillus Reuteri for Treatment of Uncomplicated UTI in Pregnant Women (UTIPregnant)

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

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

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infection in Pregnancy
• Intervention / Treatment: Dietary supplement: Probiotics; Drug: Antibiotics

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Tlalpan
    • Mexico city, Tlalpan, Mexico, 14080
      • Hospital General Dr. Manuel Gea Gonzalez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 5*10^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938, PAC-A and Zinc	Dietary supplement: Probiotics; The Probiotic group will receive Sachet 1 - contains an instant cranberry drink, consisting of xylitol, monosodium citrate, cranberry aroma, cranberry extract, grape-skin extract, xanthan gum, acesulfame potassium and zinc gluconate and Sachet 2 - contains a total of 5*10^8 CFU of Lactobacillus reuteri DSM 16666/ATCC 55845 & Lactobacillus reuteri DSM 17938, mixed with maltodextrin. Both Sachets should be administered Day 1-14, twice per day This group will also receive for Placebo for Antibiotic treatment day 1-7, twice per day
Active Comparator: Antibiotic; Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) for patients with positive nitrates in dipstick	Drug: Antibiotics; Patient in this group will receive for 7 days Amoxicillin + clavulanic acid (500 mg twice daily) for seven days in patients with negative nitrites in dipstick or oral nitrofurantoin (200mg twice per day) for patients with positive nitrates in dipstick. This group will also receive for placebo for probiotics 2 sachets for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and/or Bacteriological cure	Number of cases with improvement of symptoms severity and/or urinary culture during the first seven days of treatment	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate	Rate of recurrence cases during the rest of pregnancy	6 months
Time to relapse	Time occurred since the finish of treatment until new UTI occurred	6 months
Frequency of pyelonephritis	Number of cases of pyelonephritis in each branch	6 months
Frequency of preterm babies	Number of children at delivery with <36wekks of gestation	6 months
Antibiotic rescue	Use of antibiotics for the treatment of pyelonephritis	6 months
Adverse events	Frequency of adverse events in each branch	14 days

Collaborators and Investigators

• Sponsor: Innovacion y Desarrollo de Estrategias en Salud
• Collaborators: BioGaia AB

Publications and helpful links

General Publications

• 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.
• Colgan R, Williams M. Diagnosis and treatment of acute uncomplicated cystitis. Am Fam Physician. 2011 Oct 1;84(7):771-6.
• Colgan R, Williams M, Johnson JR. Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician. 2011 Sep 1;84(5):519-26.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): June 18, 2019

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 20, 2019
• Last Update Submitted That Met QC Criteria: June 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Urologic Diseases; Urinary Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: CSUB 0139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No