Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT) (PIVOT)

October 9, 2012 updated by: Medical Research Council

A Randomised Controlled Trial of a Strategy of Switching to Boosted PI Monotherapy Versus Continuing Combination ART for the Long-term Management of HIV-1 Infected Patients Who Have Achieved Sustained Virological Suppression on HAART

The PIVOT trial aims to determine whether a strategy of switching to PI monotherapy is non-inferior to continuing triple-therapy, in terms of the proportion of patients who maintain all the drug treatment options that were available to them at baseline after at least 3 years of follow-up, and to compare clinical events, safety, toxicity and health economic parameters between the two strategies.

Study Overview

Study Type

Interventional

Enrollment (Actual)

587

Phase

  • Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Vl < 50 for 24 weeks prior to screening CD4 > 100 at screening

Exclusion Criteria:

  1. Known major protease resistance mutation(s) documented on prior resistance testing if performed (prior resistance testing is not mandatory for trial participation).
  2. Previous change in ART drug regimen for reasons of unsatisfactory virological response (patients who have changed regimen for prevention or management of toxicity or to improve regimen convenience are permitted to enter the trial).
  3. Previous allergic reaction to a PI.
  4. Patient currently using or likely to require use of concomitant medication with known interaction with PIs.
  5. Patient requiring treatment with radiotherapy, cytotoxic chemotherapy, or is anticipated to need these during the trial period.
  6. Treatment for acute opportunistic infection within 3 months prior to trial screening.
  7. Pregnant or trying to become pregnant at the time of trial entry.
  8. History of active substance abuse or psychiatric illness that, in the opinion of the investigator, would preclude compliance with the protocol, dosing schedule or assessments.
  9. History of HIV encephalopathy with current deficit >1 in any domain of the Neuropsychiatric AIDS Rating Scale (see Appendix 7).
  10. Past or current history of cardiovascular disease, or 10 year absolute coronary heart disease risk of >30%, or risk of >20% if the patient has diabetes or a family history of premature ischaemic heart disease or stroke.
  11. History of insulin-dependent diabetes mellitus.
  12. Patient currently receiving interferon therapy for Hepatitis C virus infection or planning to start treatment for Hepatitis C at the time of trial entry.
  13. Co-infection with hepatitis B, defined as Hepatitis BsAg positive at screening or at any time since HIV diagnosis, unless the patient has had a documented Hepatitis B DNA measurement of less than 1000 copies/ml taken whilst off Hepatitis B active drugs.
  14. Any other active clinically significant condition, or findings during screening medical history or examination, or abnormality on screening laboratory blood tests that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
  15. Fasting plasma glucose >7.0mmol/L at trial screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Protease Inhibitor Monotherapy
Ritonavir-boosted protease inhibitor
Switch to a regimen comprising a single ritonavir-boosted Protease Inhibitor
Active Comparator: Control
Standard-of-care triple-therapy regimen
Regimen should consist of 3 drugs: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Loss of future drug options
Time Frame: Up to 5 years
The first occurrence of intermediate to high level resistance to any one or more of the standard antiretroviral drugs (limited to licensed drugs in contemporary use) to which the patient's virus was considered to be sensitive at trial entry (i.e. excluding drug resistance that was known to be present on previous resistance testing).
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: Up to 5 years
Up to 5 years
Death from any cause
Time Frame: Up to 5 years
Up to 5 years
Serious AIDS-defining illness
Time Frame: Up to 5 years
Up to 5 years
Serious non-AIDS defining illness
Time Frame: Up to 5 years
Up to 5 years
Confirmed Virological rebound
Time Frame: Up to 5 years
Up to 5 years
CD4+ count change
Time Frame: Up to 5 years
Up to 5 years
Health-related Quality of Life change
Time Frame: Up to 5 years
Up to 5 years
Neurocognitive function change
Time Frame: Up to 5 years
Up to 5 years
Cardiovascular risk change
Time Frame: Up to 5 years
Up to 5 years
Health care costs
Time Frame: Up to 5 years
Up to 5 years
HIV VL in Genital Secretions
Time Frame: Week 96

In a sub-set of participants (n=73):-

  • Compare prevalence of detectable VL and magnitude of viral replication in genital secretions in patients taking PI monotherapy and triple therapy; to test if PI monotherapy is non-inferior to triple therapy.
  • Compare drug levels in genital secretions and plasma.
  • Describe the profile of drug resistance (if any) in patients with detectable VL in genital secretions and to compare this with any previous or subsequent resistance profile in plasma.

(Genital Secretions substudy REC # 09/H0305/58)

Week 96
HIV VL in CSF
Time Frame: Week 96

In a subset of participants on PI monotherapy (n=40).

  • Estimate the proportion of patients who have detectable HIV viral load in CSF after 48 weeks on PI monotherapy, and to refute the hypothesis that this proportion is greater than 20%.
  • Assess whether CSF markers of CNS immune activation, inflammation and neuronal degeneration are elevated after 48 weeks on PI monotherapy.
  • Assess whether CSF HIV viral load and markers of immune activation, inflammation and neuronal degeneration are elevated in patients with symptomatic CNS disease.

(CNS substudy REC # 09/H0305/58).

Week 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Nick Paton, MD, Medical Research Council

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Anticipated)

November 1, 2013

Study Completion (Anticipated)

November 1, 2013

Study Registration Dates

First Submitted

October 27, 2010

First Submitted That Met QC Criteria

October 28, 2010

First Posted (Estimate)

October 29, 2010

Study Record Updates

Last Update Posted (Estimate)

October 10, 2012

Last Update Submitted That Met QC Criteria

October 9, 2012

Last Verified

October 1, 2010

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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