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

NCT05166746 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: AVM_Lacto_2015/582
• Study Type: interventional
• Target: 333
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Bacterial Vaginoses; Infertility, Female

Outcome Measures

Primary Outcomes (1)

• Rate of clinical pregnancy per embryo transfer

  Ultrasound scan detection of intrauterine fetal heartbeat in gestational week 7-9

  7-9 weeks

Secondary Outcomes (8)

• Cure of abnormal vaginal microbiota

  1-2 months

• Live birth rate

  25-42 weeks depending on pregnancy.

• Biochemical pregnancy

  14 days gestation

• Implantation rate

  pregnancy scan at 7-9 weeks

• early miscarriage

  14 days - 12 weeks gestation

Study Arms (3)

Clindamycin + LACTIN-V (L.crispatus)

ACTIVE COMPARATOR

Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.

Drug: Clindamycin

Clindamycin + placebo LACTIN-V

ACTIVE COMPARATOR

Oral Clindamycin 300 mg 2 times per day for 7 days followed by LACTIN-V placebo (Osel, Inc.) until completion of the clinical pregnancy scan at week 7-9.

Drug: Clindamycin

Placebo clindamycin + placebo LACTIN-V

PLACEBO COMPARATOR

Matching clindamycin placebo 2 times per day for 7 days followed by LACTIN-V placebo (Osel Inc.) until completion of the clinical pregnancy scan at week 7-9.

Other: Placebo

Interventions

Clindamycin DRUG

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

Also known as: LACTIN-V

Clindamycin + LACTIN-V (L.crispatus); Clindamycin + placebo LACTIN-V

Placebo OTHER

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

Placebo clindamycin + placebo LACTIN-V

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Peter Humaidan: lead

Study Sites (4)

Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Stork Fertility Clinic VivaNeo

Copenhagen, 2100, Denmark

RECRUITING

Hvidovre Hospital, The Fertility Clinic

Hvidovre, 2650, Denmark

RECRUITING

Fertility Clinic Skive, Skive Regional Hospital

Skive, 7800, Denmark

RECRUITING

MeSH Terms

Conditions

Vaginosis, Bacterial; Infertility, Female

Interventions

Clindamycin

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; Infertility

Intervention Hierarchy (Ancestors)

Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates

Central Study Contacts

Thor Haahr, MD

CONTACT

+4527885402; thohaa@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Moreover, an interim analysis will be performed by blinded outcomes assessors according to the primary outcome.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: December 22, 2021
• Study Start: December 7, 2017
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: July 6, 2023

Record last verified: 2023-07

Locations

DK (4)