The Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota

Infertility, Female Clinical Trial

Official title:

A Double-blind, Placebo-controlled Multicenter Trial on the Effect of Clindamycin and a Live Biotherapeutic on the Reproductive Outcomes of IVF Patients With Abnormal Vaginal Microbiota

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05166746
• Other study ID #: AVM_Lacto_2015/582
• Status: Recruiting
• Phase: Phase 2
• Start date: December 7, 2017
• Est. completion date: October 1, 2023

Study information

• Verified date: July 2023
• Source: Regionshospitalet Viborg, Skive
• Contact: Thor Haahr, MD
• Phone: +4527885402
• Email: thohaa[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study question: Does antibiotic alone or in combination with live biotherapeutic treatment of an abnormal vaginal microbiota improve the reproductive outcomes of IVF couples?

Study hypothesis:

The investigator hypothesize that treatment of the reproductive tract pathogens and restoration of vaginal Lactobacillus will improve the reproductive outcomes of IVF patients.

What is known already? Ultra-deep sequencing methods enable the refinement of reproductive tract microbiology in infertile patients. A recent meta-analysis reported that 19% of infertile patients had abnormal vaginal microbiota Moreover, someone have detected the presence of a Gardnerella (G.) vaginalis dominated endometrial biofilm in 50% of non-infertile patients with abnormal vaginal microbiota undergoing curettage; thus the treatment of such an endometrial biofilm might play an important role for the endometrial receptivity and subsequently the clinical pregnancy rate.

Pilot study: In a recent pilot study it was observed that an abnormal vaginal microbiota negatively affects the clinical pregnancy rate in IVF patients. In this study the prevalence of abnormal vaginal microbiota was 28% (36/130) and only 9% of patients with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (p=0.004). This association remained significant in an adjusted analysis. Furthermore, the invetigators have preliminary results demonstrating that vaginal bacteria such as G. vaginalis can be found in the endometrium of IVF patients, which is also supported by recent publications

What is the novelty of this study? To the investigators knowledge, no previous treatment study of abnormal reproductive tract microbiota has been performed in IVF patients; this relatively small intervention holds the potential to increase the baby-take-home rate after IVF treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 333
• Est. completion date: October 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

Inclusion Criteria:

• Abnormal vaginal microbiota.

• The screening swab should be repeated if more than 3 months old.

• HIV, Hepatitis B or C positivity.

• First, second or third IVF stimulation cycle or embryo transfer therefrom.

• BMI<35

• Written informed consent.

Exclusion Criteria:

• Known or suspected hypersensitivity to clindamycin.

• HPV CIN 2 or higher.

• Former or current inflammatory bowel disease

• Severe concomitant disease, including diabetes.

• MAX 2 embryos may be transferred

• Artificial heart valve

• Intrauterine malformations with operation indication as determined by treating physician (Polyps, Septum, fibroma)

Related Conditions & MeSH terms

• Bacterial Vaginoses
• Infertility
• Infertility, Female
• Vaginosis, Bacterial

Intervention

Drug:
• Clindamycin
Oral clindamycin 300mg/2xdaily in 7 days. LACTIN-V applicators 1x at night in 7 days, then 2xper week at night for 7 weeks.

Other:
• Placebo
The Clindamycin placebo appear identical to active clindamycin by filling capsules with Mannitolium. The LACTIN-V placebo product has no intrinsic effect and is used to study the effect of the therapeutically active product. It is supplied as a pre-filled vaginal applicator packaged under nitrogen gas with one desiccant packet (0.25 g) in a sealed foil pouch. Each applicator contains 200 mg of LACTIN-V placebo powder containing the inactive ingredients of the LACTIN-V drug product, but not Lactobacillus crispatus CTV-05 (CTV-05), the active ingedient. The excipients used in the manufacture of LACTIN-V placebo are identical to those in the LACTIN-V drug product. Each placebo applicator contains the following constituents: maltodextrin, trehalose, xylitol, colloidal silicon dioxide, and sodium ascorbate

Locations

Country	Name	City	State
Denmark	Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Stork Fertility Clinic VivaNeo	Copenhagen
Denmark	Hvidovre Hospital, The Fertility Clinic	Hvidovre
Denmark	Fertility Clinic Skive, Skive Regional Hospital	Skive

Sponsors (1)

Lead Sponsor	Collaborator
Peter Humaidan

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of clinical pregnancy per embryo transfer	Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9	7-9 weeks
Secondary	Cure of abnormal vaginal microbiota	A vaginal swab and qPCR-validated diagnostics for abnormal vaginal microbiota	1-2 months
Secondary	Live birth rate	The birth of a live born child after 25 gestational weeks.	25-42 weeks depending on pregnancy.
Secondary	Biochemical pregnancy	positive hCG blood test	14 days gestation
Secondary	Implantation rate	The number of embryos implanting	pregnancy scan at 7-9 weeks
Secondary	early miscarriage	The loss of an hCG positive pregnancy	14 days - 12 weeks gestation
Secondary	Number of late miscarriage	The of pregnancy in late pregnancy	12 weeks gestation - to labour (i.e. not including still birth)
Secondary	Number of preterm birth	birth of a liveborn	prior to 37 gestational weeks
Secondary	Birth weight	weight at birth	25-42 weeks gestation depending on pregnancy