The Ribavirin Pregnancy Registry (RPR)

• ClinicalTrials.gov Identifier: NCT00114712
• Recruitment Status: Terminated
• First Posted: June 17, 2005
• Last Update Posted: December 14, 2020
• Sponsor: Syneos Health
• Collaborators: Aurobindo Pharma Ltd; Sandoz; Merck Sharp & Dohme Corp.; Teva Pharmaceuticals USA; Zydus Pharmaceuticals USA, Inc.
• Information provided by (Responsible Party): Syneos Health

Study Description

Brief Summary:

Ribavirin should be avoided during pregnancy and during the 6 months before pregnancy in both the female and the male sexual partner. If a pregnancy occurs and is reported to the Ribavirin Pregnancy Registry, the Registry will follow the pregnant woman throughout pregnancy. The Registry will also follow the infant until 1 year of age. The goal of the Registry is to learn more about the effects of ribavirin on pregnancy and the risk for birth defects. Pregnant women exposed to ribavirin, either by taking ribavirin (during pregnancy or 6 months before pregnancy) or through a male sexual partner (who took ribavirin during the female partner's pregnancy or during the 6 months before pregnancy), are encouraged to contact the Registry.

Condition or disease
Birth Defects; Pregnancy Complications; Hepatitis C

Detailed Description:

Ribavirin, a nucleoside analog with antiviral activity, is used in combination with interferons or pegylated interferons for the treatment of chronic hepatitis C (HCV). Extensive clinical studies have demonstrated that combination therapy with ribavirin and interferons or pegylated interferons are efficacious treatments for HCV. However, ribavirin has been assigned a FDA Pregnancy Category X classification, indicating that it should not be used in women who are pregnant or in men whose partners may become pregnant. Because the incidence of HCV is highest in the group with the highest reproductive potential, the 25 - 45 year age group, (CDC, 2001) it is likely that inadvertent pregnancy exposures will occur and should be monitored. The primary objectives of this Registry are:

• To evaluate the association between ribavirin and birth defects occurring in offspring of female patients exposed to ribavirin during pregnancy or within six months after therapy has stopped.
• To evaluate the association between ribavirin and birth defects occurring in offspring of females exposed to ribavirin during pregnancy or within six months after therapy has stopped, through their male sexual partners taking ribavirin.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 477 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 12 Months
• Official Title: The Ribavirin Pregnancy Registry
• Study Start Date: January 2004
• Actual Primary Completion Date: November 2, 2020
• Actual Study Completion Date: November 2, 2020

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. To evaluate association between ribavirin and birth defects [ Time Frame: At birth outcome, infant follow-up at 6 and 12 months ]

   To evaluate the association between ribavirin and birth defects occurring in offspring of female patients exposed to ribavirin during pregnancy or within six months after therapy has stopped.

   To evaluate the association between ribavirin and birth defects occurring in offspring of females exposed to ribavirin during pregnancy or within six months after therapy has stopped, through their male sexual partners taking ribavirin.

Secondary Outcome Measures :

1. Estimate risk of birth defects in exposed pregnancies [ Time Frame: At birth outcome, infant follow-up at 6 and 12 months ]

   Attempt to estimate the risk of birth defects occurring in offspring of female patients exposed to ribavirin during pregnancy or within six months after therapy has stopped, and detect any increase in the prevalence or pattern of birth defects among these pregnancies.

   Attempt to estimate the risk of birth defects occurring in offspring of females exposed to ribavirin during pregnancy or within six months after therapy has stopped, through their male sexual partners taking ribavirin, to detect any increase in the prevalence or pattern of birth defects among these pregnancies.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Primary Analysis - US

Criteria

Inclusion Criteria:

• Pregnancy occurring to one of the following groups while the patient or sexual partner was on ribavirin and/or within six months after therapy stopped:

  • Female patients who become pregnant on ribavirin therapy, or
  • Female patients who start ribavirin therapy while pregnant, or
  • Female patients who become pregnant post-ribavirin therapy (defined as the six month time period after therapy has stopped) or
  • Females who become pregnant while their male sexual partner is on ribavirin therapy or
  • Females who are pregnant when their male sexual partner starts ribavirin therapy, or
  • Females who become pregnant while their male sexual partner is in the post-ribavirin therapy period (defined as the six month time period after therapy has stopped).
• Timing of the prenatal exposure to ribavirin, no broader than within six months prior to pregnancy or trimester during which the exposure took place.
• Sufficient information to determine whether the pregnancy is prospectively registered (i.e., whether the outcome of pregnancy was known at the time of the report).
• Date the pregnancy exposure report is registered.
• Source of the report (health care professional, pregnant patient, or male sexual partner).
• Report contact information to allow for follow-up.

Exclusion Criteria:

• Females who were not exposed to Ribavirin during the designated time (described above)

Contacts and Locations

Locations

United States, North Carolina

INC Research, LLC

Wilmington, North Carolina, United States, 28405

Sponsors and Collaborators

Syneos Health

Aurobindo Pharma Ltd

Sandoz

Merck Sharp & Dohme Corp.

Teva Pharmaceuticals USA

Zydus Pharmaceuticals USA, Inc.

Investigators

• Principal Investigator: Susan Sinclair, PhD; Syneos Health

More Information

Additional Information:

Ribavirin Pregnancy Registry web site 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sinclair SM, Jones JK, Miller RK, Greene MF, Kwo PY, Maddrey WC. The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment. Drug Saf. 2017 Dec;40(12):1205-1218. doi: 10.1007/s40264-017-0566-6.

• Responsible Party: Syneos Health
• ClinicalTrials.gov Identifier: NCT00114712
• Other Study ID Numbers: RPR-1
• First Posted: June 17, 2005
• Last Update Posted: December 14, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: A condensed version of the annual interim report is available to healthcare providers upon request.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Syneos Health:

Birth Defects; Pregnancy; Ribavirin; Hepatitis C

Additional relevant MeSH terms:

Hepatitis C; Hepatitis; Pregnancy Complications; Congenital Abnormalities; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; RNA Virus Infections; Flaviviridae Infections