PRJ2203: Dolutegravir Post Authorization Safety Study (PASS)

NCT03327740 | Completed

• 2 other identifiers: 201177PRJ2203
• Study Type: observational
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

Dolutegravir (DTG) is recommended for both treatment-naïve and treatment-experienced, HIV infected adults and paediatric subjects aged 12 years and older and weighing at least 40 kg. One case of suspected DTG hypersensitivity (HSR) reaction from among over 1500 subjects exposed to the drug at the time of submission in 4Q2012, has been identified; this subject experienced a diffuse maculopapular rash with fever and elevated liver enzymes. Isolated rash was uncommon in the DTG programme with less than 1% of clinical trial subjects experiencing treatment related rash. The pharmacovigilance strategy for DTG and DTG-containing products is to implement a post-marketing risk management program to further quantify the risk of HSR and compare it to that of other integrase inhibitors, and to possibly determine associated risk factors. In addition, the post-authorization safety study will monitor and compare hepatotoxicity and severe skin rash following initiation of DTG or other integrase inhibitor (raltegravir (RAL) or elvitegravir (EGV) based antiretroviral regimens (ARV). Further to be able to distinguish the above symptoms and reactions caused by DTG or the other integrase inhibitor regimen from that of abacavir (ABC), known to cause hypersensitivity reaction, the integrase inhibitor groups will be compared in combinations with and without ABC. This five year-long safety study will be conducted through collaboration with EuroSIDA, a well established prospective observational cohort study of more than 18,200 subjects followed in 107 hospitals in 31 European countries, plus Israel and Argentina. This is a five year-long non-interventional prospective cohort study nested within the EuroSIDA study. The study population will include HIV positive subjects over the age of 16 years from EuroSIDA clinical sites, who are new users of DTG or other integrase inhibitors with and without ABC. Following initiation of DTG with ABC based antiretroviral regimen or DTG without ABC or regimens containing other integrase inhibitors (RAL, EGV) with or without ABC or any other DTG based ARV regimen as monotherapy or two-drug regimens, the study will aim to a) Monitor and compare hypersensitivity reaction, b) Monitor and compare hepatotoxicity, and c) Monitor and compare severe skin rash among all subjects discontinuing DTG or other integrase inhibitor regimens for any reason.

Conditions

Infection, Human Immunodeficiency Virus I

Keywords

Hypersensitivity reactions (HSR); HIV; Dolutegravir

Outcome Measures

Primary Outcomes (2)

• Number of subjects with occurrence of hypersensitivity reactions (HSR), of any grade

  Hypersensitivity reactions including fever, rash, gastrointestinal symptoms, constitutional symptoms, respiratory symptoms and eosinophilia will be summarized.

  Up to 5 years

• Number of subjects with hepatic dysfunction

  Hepatic dysfunction will be indicated by liver chemistry tests

  Up to 5 years

Study Arms (5)

Subjects on DTG based ARV with ABC

These are subjects who begin a DTG based ARV regimen that includes ABC

Drug: DTG based ARV regimen with ABC

Subjects that start DTG based ARV regimen but without ABC

These are subjects who begin a DTG-based ARV regimen that does not contain ABC

Drug: DTG based ARV regimen without ABC

Subjects on other integrase inhibitor based regimen with ABC

These are subjects who begin other integrase inhibitor based regimens (RAL and EGV) that contains ABC

Drug: RAL or EGV based ARV regimens with ABC

Subjects on other integrase inhibitor based regimen but no ABC

These are subjects that start non-ABC containing RAL or EGV based regimens

Drug: RAL or EGV based regimens without ABC

Subjects that start any other DTG based ARV regimen

These are subjects who begin any other DTG based ARV regimen that will include DTG as monotherapy or two-drug regimens

Drug: Any other DTG based ARV regimen as monotherapy

Interventions

DTG based ARV regimen with ABC DRUG

ARV regimens containing DTG and ABC

Subjects on DTG based ARV with ABC

DTG based ARV regimen without ABC DRUG

DTG based ARV regimens that do not contain ABC

Subjects that start DTG based ARV regimen but without ABC

RAL or EGV based ARV regimens with ABC DRUG

RAL or EGV based regimens containing ABC

Subjects on other integrase inhibitor based regimen with ABC

RAL or EGV based regimens without ABC DRUG

RAL or EGV based ARV regimens that do not contain ABC

Subjects on other integrase inhibitor based regimen but no ABC

Any other DTG based ARV regimen as monotherapy DRUG

Any other DTG based ARV regimens including DTG as monotherapy or two-drug regimens.

Subjects that start any other DTG based ARV regimen

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV positive subjects over the age of 16 years from EuroSIDA clinical sites, who are new users of DTG or users of other integrase inhibitor regimens (RAL and EGV).

You may qualify if:

• New users of DTG or users of other integrase inhibitor regimens (RAL and EGV)

You may not qualify if:

• None

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Conditions

Infections; Hypersensitivity

Interventions

abacavir

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: October 31, 2017
• Study Start: September 30, 2014
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 6, 2020

Record last verified: 2020-02