Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
This study is ongoing, but not recruiting participants.
Sponsor:
Medical Research Council
Collaborator:
NHS Health Technology Assessment Programme
Information provided by:
Medical Research Council
ClinicalTrials.gov Identifier:
NCT01230580
First received: October 27, 2010
Last updated: October 9, 2012
Last verified: October 2010
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infection Acquired Immunodeficiency Syndrome |
Drug: Protease Inhibitor Drug: Standard-of-care Antiretroviral therapy |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Medical Research Council:
Primary Outcome Measures:
- Loss of future drug options [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]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).
Secondary Outcome Measures:
- Death from any cause [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Serious AIDS-defining illness [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Serious non-AIDS defining illness [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Adverse events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Confirmed Virological rebound [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- CD4+ count change [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Health-related Quality of Life change [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Neurocognitive function change [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Cardiovascular risk change [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Health care costs [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- HIV VL in Genital Secretions [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
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)
- HIV VL in CSF [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
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).
| Enrollment: | 587 |
| Study Start Date: | November 2008 |
| Estimated Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Protease Inhibitor Monotherapy
Ritonavir-boosted protease inhibitor
|
Drug: Protease Inhibitor
Switch to a regimen comprising a single ritonavir-boosted Protease Inhibitor
|
|
Active Comparator: Control
Standard-of-care triple-therapy regimen
|
Drug: 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
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
Vl < 50 for 24 weeks prior to screening CD4 > 100 at screening
Exclusion Criteria:
- Known major protease resistance mutation(s) documented on prior resistance testing if performed (prior resistance testing is not mandatory for trial participation).
- 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).
- Previous allergic reaction to a PI.
- Patient currently using or likely to require use of concomitant medication with known interaction with PIs.
- Patient requiring treatment with radiotherapy, cytotoxic chemotherapy, or is anticipated to need these during the trial period.
- Treatment for acute opportunistic infection within 3 months prior to trial screening.
- Pregnant or trying to become pregnant at the time of trial entry.
- 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.
- History of HIV encephalopathy with current deficit >1 in any domain of the Neuropsychiatric AIDS Rating Scale (see Appendix 7).
- 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.
- History of insulin-dependent diabetes mellitus.
- Patient currently receiving interferon therapy for Hepatitis C virus infection or planning to start treatment for Hepatitis C at the time of trial entry.
- 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.
- 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.
- Fasting plasma glucose >7.0mmol/L at trial screening.
Contacts and Locations More Information
Additional Information:
No publications provided
| Responsible Party: | Medical Research Council (Dr Nick Paton Chief Investigator MRC Clinical Trials Unit), Medical Research Council |
| ClinicalTrials.gov Identifier: | NCT01230580 History of Changes |
| Other Study ID Numbers: | PIVOT, 2007-006448-23 |
| Study First Received: | October 27, 2010 |
| Last Updated: | October 9, 2012 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Medical Research Council:
|
Protease Inhibitors RNA virus infections Virus diseases Sexually Transmitted Diseases viral |
Immune system diseases Anti-infective Agents Drug resistance |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases |
Anti-Infective Agents Protease Inhibitors Reverse Transcriptase Inhibitors Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Anti-Retroviral Agents Antiviral Agents |
ClinicalTrials.gov processed this record on June 18, 2013