Short Course Rifapentine and Isoniazid for the Preventive Treatment for Latent Genital Tuberculosis (SCRIPT-LGTB)

Fudan University

Status and phase: Unknown; Phase 3

Conditions: Genital Tuberculosis, Latent; Genital Tuberculoses, Female; Recurrent Implantation Failure; Infertility, Female

Treatments: Drug: rifapentine plus isoniazid

Study type: Interventional

Funder types: Other

Identifiers

NCT04528277

KS20232

Details and patient eligibility

About

The purpose of this study is to assess the efficacy, safety and tolerability of the 1-month regimen of three times weekly rifapentine plus isoniazid in improving fertility outcome in recurrent implantation failure (RIF) patients with latent genital tuberculosis (LGTB), compared to no treatment and non-LGTB patients.

Full description

The prevalence of latent genital tuberculosis (LGTB) is relatively high in women with infertility and recurrent pregnancy loss. Whether preventive treatment of latent tuberculosis infection (LTBI) can improve the fertility outcome in women with recurrent implantation failure (RIF) remains to be explored.

This is a prospective interventional cohort study.The main purpose of this study is to compare the fertility outcome between 1-month regimen of three times weekly rifapentine plus isoniazid and no treatment in RIF patients with LGTB and RIF patients without LGTB. The study will also assess the safety and tolerability and the efficacy of the preventive treatment regimen in prevention of the incidence of active female genital tuberculosis (FGTB).

A total of 1050 participants will be recruited for screening of LGTB. The endometrial tuberculosis (TB) polymerase chain reaction (PCR) test will be employed for the diagnosis of LGTB. Eligible participants with negative TB PCR results will be assigned to the non-LGTB group, while those with positive TB PCR results will be assigned to the LGTB group. The LGTB group will be further assigned, according to their will to receive preventive treatment of tuberculosis, to one of the following groups: the LGTB treatment group and the LGTB no treatment group.

The LGTB treatment group will receive the 1-month regimen of three times weekly rifapentine plus isoniazid, and the in vitro fertilization (IVF)/ intra cytoplasmic sperm injection (ICSI) cycle can be started after 1 month post the completion of the treatment regimen. Adverse events and side effects will be monitored at a 2-week interval during the preventive treatment and followed up once more at 4 weeks post the end of treatment. The LGTB no treatment group and the non-LGTB group will start the IVF/ICSI cycle directly after enrollment without taking any medication related to preventive treatment of tuberculosis.

Eligible participants will be followed up until the end of an IVF/ ICSI cycle or pregnancy. Fertility outcomes of both groups will be recorded and compared. Secondary outcomes, including the incidence of adverse events, the adhesion of treatment and the incidence of LGTB and FGTB, ovarian reserve, embryo quality, history of infertility and tuberculosis will also be recorded and compared.

Enrollment: 1,050 estimated patients

Sex: Female

Ages: 25 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Women aged 25-40 years old
2. Infertile women failed to achieve clinical pregnancy after 4 good quality embryo transfers, with at least 3 fresh or frozen IVF cycles
3. Intended to undergo IVF/ICSI
4. Ultrasonography or hysterosalpingogram showed a normal uterus cavity, and the thickness of the endometrium was ≥8mm before implantation during last IVF/ICSI cycle
5. Patients who voluntarily signed the informed consent and agreed to be followed up as required by the study protocol

Exclusion criteria

1. Use of donor eggs/sperm
2. An abnormal uterine cavity shown on hysterosalpingogram or hysteroscopy
3. Proven tubal infertility
4. Proven preimplantation genetic abnormality
5. Proven active tuberculosis
6. Treated for active tuberculosis or used preventive treatment for LTBI within 2 years
7. Being allergic or intolerant of any study drug
8. HIV antibody positive and AIDS patients
9. Patients with impaired liver function: hepatic encephalopathy, ascites; total bilirubin is more than 2 times higher than the upper limit of normal; alanine transaminase (ALT) or aspartate aminotransferase (AST) is more than 5 times the upper limit of normal
10. Patients with diabetes mellitus
11. Critically ill patients, and according to the judgment of the research physician, it is impossible to survive for more than 16 weeks
12. Currently participating in another drug clinical trial

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,050 participants in 3 patient groups

LGTB treatment group

Experimental group

Description:

The LGTB treatment group will receive the 1-month regimen of three times weekly rifapentine (150mg per capsule, 450mg po tiw) plus isoniazid (100mg per tablet, 400mg po tiw).

Treatment:

Drug: rifapentine plus isoniazid

LGTB no treatment group

No Intervention group

Description:

The LGTB no treatment group will not take any medication related to preventive treatment of tuberculosis.

non-LGTB group

No Intervention group

Description:

The non-LGTB group will not take any medication related to preventive treatment of tuberculosis.