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

Role of Short Course Rifapentine and Isoniazid for the Preventive Treatment for Latent Genital Tuberculosis in Women With Recurrent Implantation Failure: A Prospective Interventional Cohort Study

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.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female; Recurrent Implantation Failure; Genital Tuberculoses, Female; Genital Tuberculosis, Latent
• Intervention / Treatment: Drug: rifapentine plus isoniazid

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 1050
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200051
      • Shanghai first maternity and infant hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LGTB treatment group; 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).	Drug: rifapentine plus isoniazid; receive the 1-month regimen of three times weekly rifapentine (450mg po) plus isoniazid (400mg po)
No Intervention: LGTB no treatment group; The LGTB no treatment group will not take any medication related to preventive treatment of tuberculosis.
No Intervention: non-LGTB group; The non-LGTB group will not take any medication related to preventive treatment of tuberculosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rates	Clinical pregnancy was defined as the presence of at least one gestational sac on ultrasound at 6 weeks.	6 weeks after completion of an IVF/ICSI cycle
Ongoing Pregnancy Rate	Ongoing pregnancy was the presence of at least one foetus with heart pulsation on ultrasound beyond 10 weeks.	10 weeks after completion of an IVF/ICSI cycle
Miscarriage rate	The number of miscarriages before 22 weeks divided by the number of participants with positive pregnancy test.	22 weeks after completion of an IVF/ICSI cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	The number of gestational sacs seen on scanning divided by the number of embryos replaced.	6 weeks after completion of an IVF/ICSI cycle
Incidence of LGTB	The number of participants diagnosed with LGTB devided by the number of participants screened for LGTB.	4 weeks after enrollment
Incidence of FGTB	The number of participants developed FGTB during treatment or follow-up devided by the number of participants in the LGTB treatment group.	2 years
Incidence of grade 3 or greater adverse events	The number of participants reported grade 3 or greater adverse events during treatment or follow-up devided by the number of participants in the LGTB treatment group.	20 weeks after preventive treatment initiated
Completion rate of preventive treatment	11 or 12 doses of the 1-month preventive treatment regimen of three times weekly rifapentine plus isoniazid taken within 16 weeks after treatment initiated will be regarded as completion of preventive treatment. The number of participants completed treatment devided by the number of participants initiated the preventive treatment.	20 weeks after preventive treatment initiated
Discontinuation of treatment	The number of participants discontinued treatment devided by the number of participants in the LGTB treatment group.	20 weeks after preventive treatment initiated
Discontinuation of treatment due to side effect of study drugs	The number of participants discontinued treatment due to side effect of study drugs devided by the number of participants in the LGTB treatment group.	20 weeks after preventive treatment initiated

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai First Maternity and Infant Hospital

Publications and helpful links

General Publications

• Grace GA, Devaleenal DB, Natrajan M. Genital tuberculosis in females. Indian J Med Res. 2017 Apr;145(4):425-436. doi: 10.4103/ijmr.IJMR_1550_15.
• Jindal UN, Verma S, Bala Y. Favorable infertility outcomes following anti-tubercular treatment prescribed on the sole basis of a positive polymerase chain reaction test for endometrial tuberculosis. Hum Reprod. 2012 May;27(5):1368-74. doi: 10.1093/humrep/des076. Epub 2012 Mar 14.
• Dam P, Shirazee HH, Goswami SK, Ghosh S, Ganesh A, Chaudhury K, Chakravarty B. Role of latent genital tuberculosis in repeated IVF failure in the Indian clinical setting. Gynecol Obstet Invest. 2006;61(4):223-7. doi: 10.1159/000091498. Epub 2006 Feb 13.
• Jirge PR, Chougule SM, Keni A, Kumar S, Modi D. Latent genital tuberculosis adversely affects the ovarian reserve in infertile women. Hum Reprod. 2018 Jul 1;33(7):1262-1269. doi: 10.1093/humrep/dey117.
• Bagchi B, Chatterjee S, Gon Chowdhury R. Role of latent female genital tuberculosis in recurrent early pregnancy loss: A retrospective analysis. Int J Reprod Biomed. 2019 Dec 30;17(12):929-934. doi: 10.18502/ijrm.v17i12.5799. eCollection 2019 Dec.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: August 22, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis, Urogenital; Infertility; Tuberculosis; Latent Tuberculosis; Infertility, Female; Tuberculosis, Female Genital; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Antitubercular Agents; Antibiotics, Antitubercular; Fatty Acid Synthesis Inhibitors; Rifapentine; Isoniazid
• Other Study ID Numbers: KS20232

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
• product manufactured in and exported from the U.S.: No