Ruth N Moro1,2, Nigel A Scott1,2, Andrew Vernon1, Naomi K Tepper1, Stefan V Goldberg1, Kevin Schwartzman3, Chi-Chiu Leung4, Neil W Schluger5, Robert W Belknap6, Richard E Chaisson7, Masahiro Narita8,9, Elizabeth S Machado10, Marta Lopez11, Jorge Sanchez12,13, Margarita E Villarino1, Timothy R Sterling14. 1. 1 Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. 2. 2 CDC Foundation Research Collaboration, Atlanta, Georgia. 3. 3 McGill University Health Centre, Respiratory Epidemiology and Clinical Research Unit, Montreal, Quebec, Canada. 4. 4 Tuberculosis and Chest Service, Department of Health, Hong Kong, China. 5. 5 Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, New York. 6. 6 Denver Health and Hospitals, Denver, Colorado. 7. 7 Johns Hopkins University School of Medicine, Center for Tuberculosis Research, Baltimore, Maryland. 8. 8 Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington. 9. 9 Tuberculosis Control Program Public Health, King County, Seattle, Washington. 10. 10 Universidad Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 11. 11 Maternal-Fetal Medicine Department, Hospital Clinic and Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain. 12. 12 Asociación Civil IMPACTA Salud y Educación, Lima, Peru. 13. 13 Department of Global Health, University of Washington, Seattle, Washington; and. 14. 14 Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract
RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS:Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).
RCT Entities:
RATIONALE: Data are limited regarding the safety of 12-dose once-weekly isoniazid (H, 900 mg) plus rifapentine (P, 900 mg) (3HP) for latent infection treatment during pregnancy. OBJECTIVES: To assess safety and pregnancy outcomes among pregnant women who were inadvertently exposed to study medications in two latent tuberculosis infection trials (PREVENT TB or iAdhere) evaluating 3HP and 9 months of daily isoniazid (H, 300 mg) (9H). METHODS: Data from reproductive-age (15-51 yr) women who received one or more study dose of 3HP or 9H in either trial were analyzed. Drug exposure during pregnancy occurred if the estimated date of conception was on or before the last dose date. RESULTS: Of 126 pregnancies (125 participants) that occurred during treatment or follow-up, 87 were exposed to study drugs. Among these, fetal loss was reported for 4/31 (13%) and 8/56 (14%), 3HP and 9H, respectively (difference, 13% - 14% = -1%; 95% confidence interval = -17% to +18%) and congenital anomalies in 0/20 and 2/41 (5%) live births, 3HP and 9H, respectively (difference, 0% - 5% = -5%; 95% confidence interval = -18% to +16%). All fetal losses occurred in pregnancies of less than 20 weeks. Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportion of fetal loss (17/126 [13%]) and anomalies (3/93 [3%]) were similar to those estimated for the United States, 17% and 3%, respectively. CONCLUSIONS: Among reported pregnancies in these two latent tuberculosis infection trials, there was no unexpected fetal loss or congenital anomalies. These data offer some preliminary reassurance to clinicians and patients in circumstances when these drugs and regimens are the best option in pregnancy or in women of child-bearing potential. This work used the identifying trial registration numbers NCT00023452 and NCT01582711, corresponding to the primary clinical trials PREVENT TB and iAdhere (Tuberculosis Trials Consortium Study 26 and 33).
Authors: A C Crampin; J R Glynn; S Floyd; S S Malema; V K Mwinuka; B M M Ngwira; F D Mwaungulu; D K Warndorff; P E M Fine Journal: Int J Tuberc Lung Dis Date: 2004-02 Impact factor: 2.373
Authors: Roque Miramontes; Andrew N Hill; Rachel S Yelk Woodruff; Lauren A Lambert; Thomas R Navin; Kenneth G Castro; Philip A LoBue Journal: PLoS One Date: 2015-11-04 Impact factor: 3.240
Authors: Sylvia M LaCourse; Anjuli D Wagner; Lisa M Cranmer; Audrey Copeland; Elizabeth Maleche-Obimbo; Barbra A Richardson; Daniel Matemo; John Kinuthia; Grace John-Stewart Journal: J Acquir Immune Defic Syndr Date: 2019-09-01 Impact factor: 3.731
Authors: Anthony D Harries; Ajay M V Kumar; Srinath Satyanarayana; Pruthu Thekkur; Yan Lin; Riitta A Dlodlo; Mohammed Khogali; Rony Zachariah Journal: Trop Med Infect Dis Date: 2020-04-16
Authors: Amita Gupta; Michael D Hughes; Anthony J Garcia-Prats; Katherine McIntire; Anneke C Hesseling Journal: PLoS Med Date: 2019-08-15 Impact factor: 11.069