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

HIV Infection Clinical Trial

— PIVOT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01230580
• Other study ID #: PIVOT
• Secondary ID: 2007-006448-23
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 27, 2010
• Last updated: October 9, 2012
• Start date: November 2008
• Est. completion date: November 2013

Study information

• Verified date: October 2010
• Source: Medical Research Council
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 587
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infection
• HIV Infections
• Immunologic Deficiency Syndromes
• Infection

Intervention

Drug:
• Protease Inhibitor
Switch to a regimen comprising a single ritonavir-boosted Protease Inhibitor
• Standard-of-care Antiretroviral therapy
Regimen should consist of 3 drugs: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Medical Research Council	NHS Health Technology Assessment Programme

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Loss of future drug options	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	No
Secondary	Death from any cause		Up to 5 years	No
Secondary	Serious AIDS-defining illness		Up to 5 years	No
Secondary	Serious non-AIDS defining illness		Up to 5 years	No
Secondary	Adverse events		Up to 5 years	Yes
Secondary	Confirmed Virological rebound		Up to 5 years	No
Secondary	CD4+ count change		Up to 5 years	Yes
Secondary	Health-related Quality of Life change		Up to 5 years	No
Secondary	Neurocognitive function change		Up to 5 years	Yes
Secondary	Cardiovascular risk change		Up to 5 years	Yes
Secondary	Health care costs		Up to 5 years	No
Secondary	HIV VL in Genital Secretions	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	No
Secondary	HIV VL in CSF	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	No

External Links

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