HIV InfectionPhase 4PIVOTNCT01230580
Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
A Phase 4 study testing Protease Inhibitor and Standard-of-care Antiretroviral therapy in people with HIV Infection and Acquired Immunodeficiency Syndrome, run by Medical Research Council.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, Acquired Immunodeficiency Syndrome
- What is being tested?
- Protease Inhibitor and Standard-of-care Antiretroviral therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 587 participants
- Where
- No sites listed yet
- Study dates
- Nov 2008to Nov 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Vl < 50 for 24 weeks prior to screening CD4 > 100 at screening
Who cannot join
- 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.
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- 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.
About this study
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
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.
- Conditions
- HIV Infection, Acquired Immunodeficiency Syndrome
- Being tested
- Protease Inhibitor, Standard-of-care Antiretroviral therapy
- Keywords
- Protease Inhibitors, RNA virus infections, Virus diseases, Sexually Transmitted Diseases viral, Immune system diseases, Anti-infective Agents, Drug resistance
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome, RNA Virus Infections, Virus Diseases, Sexually Transmitted Diseases, Viral, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protease InhibitorDrug
Switch to a regimen comprising a single ritonavir-boosted Protease Inhibitor
Standard-of-care Antiretroviral therapyDrug
Regimen should consist of 3 drugs: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Protease Inhibitor Monotherapy | Experimental | Ritonavir-boosted protease inhibitor Receives: Drug: Protease Inhibitor |
| Control | Active comparator | Standard-of-care triple-therapy regimen Receives: Drug: Standard-of-care Antiretroviral therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 5 years
Secondary outcomes (12)
Death from any cause
Measured: Up to 5 years
Serious AIDS-defining illness
Measured: Up to 5 years
Serious non-AIDS defining illness
Measured: Up to 5 years
Adverse events
Measured: Up to 5 years
Confirmed Virological rebound
Measured: Up to 5 years
CD4+ count change
Measured: Up to 5 years
Health-related Quality of Life change
Measured: Up to 5 years
Neurocognitive function change
Measured: Up to 5 years
Cardiovascular risk change
Measured: Up to 5 years
Health care costs
Measured: Up to 5 years
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)
Measured: Week 96
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).
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2010 (estimated)
- Study startNov 2008
- Primary completionNov 2013 (estimated)
- Study completionNov 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 587 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Research Council
- Sponsor type
- Other government
- Collaborators
- NHS Health Technology Assessment Programme
- Investigators
- Nick Paton, MD, Principal investigator, Medical Research Council
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230580
- Sponsor's protocol ID
- PIVOT
- Other IDs
- 2007-006448-23
- Acronym
- PIVOT
- Status last verified
- Oct 2010
- First submitted
- 27 Oct 2010
- Last updated
- 10 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Winston A, Arenas-Pinto A, Stohr W, Fisher M, Orkin CM, Aderogba K, De Burgh-Thomas A, O'Farrell N, Lacey CJ, Leen C, Dunn D, Paton NI; PIVOT Trial Team. Neurocognitive function in HIV infected patients on antiretroviral therapy. PLoS One. 2013 Apr 30;8(4):e61949. doi: 10.1371/journal.pone.0061949. Print 2013.
PubMed 23646111
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01230580
- Acronym / sponsor ID
- PIVOT / PIVOT
- Conditions
- HIV Infection, Acquired Immunodeficiency Syndrome
- Keywords
- Protease Inhibitors, RNA virus infections, Virus diseases, Sexually Transmitted Diseases viral, Immune system diseases, Anti-infective Agents, Drug resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 587 participants (actual)
- Lead sponsor
- Medical Research CouncilOther government
- Collaborators
- NHS Health Technology Assessment Programme
- Study start
- Nov 2008
- Primary completion
- Nov 2013 (estimated)
- Study completion
- Nov 2013 (estimated)
- First posted
- 29 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protease Inhibitor Monotherapy | Experimental | Drug: Protease InhibitorRitonavir-boosted protease inhibitor |
| Control | Active comparator | Drug: Standard-of-care Antiretroviral therapyStandard-of-care triple-therapy regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Vl < 50 for 24 weeks prior to screening CD4 > 100 at screening
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protease InhibitorSwitch to a regimen comprising a single ritonavir-boosted Protease Inhibitor | Drug | Protease Inhibitor Monotherapy |
| Standard-of-care Antiretroviral therapyRegimen should consist of 3 drugs: 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor | Drug | Control |
Primary outcome
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).
12 secondary outcomes
Death from any cause
Time frame: Up to 5 years
Serious AIDS-defining illness
Time frame: Up to 5 years
Serious non-AIDS defining illness
Time frame: Up to 5 years
Adverse events
Time frame: Up to 5 years
Confirmed Virological rebound
Time frame: Up to 5 years
CD4+ count change
Time frame: Up to 5 years
Health-related Quality of Life change
Time frame: Up to 5 years
Neurocognitive function change
Time frame: Up to 5 years
Cardiovascular risk change
Time frame: Up to 5 years
Health care costs
Time frame: Up to 5 years
HIV VL in Genital Secretions
Time frame: Week 96
HIV VL in CSF
Time frame: Week 96
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2012.
- Derived from this study: PubMed 23646111Winston A, Arenas-Pinto A, Stohr W, Fisher M, Orkin CM, Aderogba K, De Burgh-Thomas A, O'Farrell N, Lacey CJ, Leen C, Dunn D, Paton NI; PIVOT Trial Team. Neurocognitive function in HIV infected patients on antiretroviral therapy. PLoS One. 2013 Apr 30;8(4):e61949. doi: 10.1371/journal.pone.0061949. Print 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nick Paton, MD principal investigator
Medical Research Council
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Protease Inhibitor and Standard-of-care Antiretroviral therapy in people with HIV Infection and Acquired Immunodeficiency Syndrome, run by Medical Research Council.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Loss of future drug options (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01230580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2012.