HIV InfectionsPhase 4MOSTNCT00531986
HIV - Monotherapy in Switzerland (MOST-ch)
A Phase 4 study testing Lopinavir-Monotherapy and HAART in people with HIV Infections, run by Cantonal Hospital of St. Gallen at 6 sites in Switzerland.
Trial summary
The investigators plan to conduct a two arm study, to compare failure rates in the central nervous system (CNS) and genital compartment in virologically fully suppressed patients continuing a highly active antiretroviral therapy (HAART) versus patients switching to ritonavir boosted lopinavir (Kaletra®)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Lopinavir-Monotherapy and HAART
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 6 sitesSwitzerland
- Study dates
- Jan 2007to Dec 2008
- 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
- Age > 18 years.
- HIV seropositive.
- HAART (> 6 months) with at least 3 months successfully suppressed HIV- RNA (two most recent RNA measurements < 50 cp/ml). HAART is defined as either:
- 1 PI plus 2 NRTIs,
- 1 NNRTI plus 2 NRTIs, or
- 3 NRTIs.
Show all 11Show fewer
- HIV-RNA in plasma < 50 cp/ml at screening.
- Stable antiretroviral therapy (unchanged drug combination) during the last four weeks.
- If not currently on a LPV/ r based therapy, willing to switch to LPV/ r bid therapy in case patient is randomized to the monotherapy arm
- Signed written informed consent.
- Highly motivated patients able to understand the investigational nature of this open observational study and willing to participate in additional procedures.
Who cannot join
- Other investigational substance or substances active against HIV.
- Previous history of adverse events with the drugs under investigation.
- Previous history of any virological treatment failure (does not include deliberate treatment interruption) or documented resistance against the drugs under investigation (LPV/r).
- Patient who has no effective alternative treatment options in case the study treatment fails (according to the physician's judgment).
- Pregnancy (negative pregnancy test for women of childbearing potential at screening).
- Active AIDS-defining disease necessitating antibiotic or chemotherapy at the time of screening.
- Chronic hepatitis B.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Switzerland6 sites
Nuesch
Basel, Petersgraben 4, 4031
Furrer
Bern, INF KP PKT 2B Freiburgstr., 3010
Hirschel
Geneva, 1211
Cavassini
Lausanne, Rue Du Bugnon 21, 1005
Flepp
Zurich, Bellariastrasse 38, 8038
Opravil
Zurich, Rämistrasse 100, 8091
About this study
Official title: HIV- Monotherapy in Switzerland (MOST- ch)
The investigators plan to conduct a two arm study, to compare failure rates in the central nervous system (CNS) and genital compartment in virologically fully suppressed patients continuing a highly active antiretroviral therapy (HAART) versus patients switching to ritonavir boosted lopinavir (Kaletra®) HIV-monotherapy. The study is composed of two phases of 48 weeks duration.
In addition, neuropsychological tests (Color trial test A 1 and 2; Grooved pegboard; EWIA Digit Symbol form) and evaluation of side effects will be performed.
Read the detailed description
In the first phase (phase A), ritonavir-boosted lopinavir (Kaletra®) will be compared with continued HAART. In the second year (phase B) patients on conventional HAART are also offered LPV/r monotherapy to extend the longterm experience of this new strategy.
Only patients willing to give a genital secretion and a spinal fluid sample will be included. All patients must be on a fully suppressive HAART with at least 2 consecutive values of HIV-RNA at the screening visit . After performance of lumbar puncture at baseline, patients will be randomized to continued HAART or LPV/r monotherapy. During the first year of randomized treatment patients will be followed at week 6/ 12 /18 /24 /32 /40 and 48. Lumbar puncture and genital secretion sampling will be repeated at week 48.
Follow up during the second phase (B: W48-96) of the study will be identical to phase A including genital and spinal sampling at week 96. After study termination at week 96, patients may opt to continue monotherapy if results of HIV-RNA in blood and CSF support this decision.
The primary endpoint of the study will be treatment failure in the compartment (CSF and / or genital tract). Since the variability of HIV-RNA determination in CSF and genital secretions is not very well known, a one log increase above the baseline value will be considered as treatment failure in the respective compartment. Only patients who had a complete viral suppression in blood will be considered for compartment evaluation. Patients treated in the monotherapy arm with a CSF HIV-RNA value at week 48 more than 1.0 log10 cp/ml above baseline (= compartment failure) will be switched to a conventional combination treatment. HIV-RNA testing in the genital samples will be performed batchwise at the end of the study.
In addition, patients with a blood treatment failure (two consecutive HIV-RNA detections > 400cp/ml) will be considered as full treatment failures and switched to a rescue regimen at the discretion of the treating physician. For the analysis, these patients will be considered as systemic treatment failure and will not be entered in the analysis of compartmentalized treatment failure. If the rescue strategy was only intensification of adherence and results in full blood viral load re-suppression, the patient will still be maintained in the study and compartment evaluations can be performed at w48 and/or 96, respectively.
The secondary aim of the study is the definition of prognostic markers for compartment failures. Potential risk factors associated with mono-maintenance failure are HIV-DNA load at time of treatment simplification, HIV-RNA at the time of first treatment initiation, duration of HIV-RNA suppression before simplification, history of HIV-RNA blips, presence of detectable HIV-RNA in spinal fluid at the time of treatment simplification, changes of level of c-reactive protein (high sensitive methodology, hsCRP) from baseline as a marker of immune-activation during the maintenance therapy.
If funding allows, we will test for the presence of resistant viruses and compare the presence of genetic polymorphism at baseline. We will also measure parameters of immunoactivation (hsCRP, CD8+, CD38+).
The study is financed by the Swiss National Science Foundation and the Swiss HIV Cohort Study.
- Conditions
- HIV Infections
- Being tested
- Lopinavir-Monotherapy, HAART
- Keywords
- Monotherapy, Neuropsychological tests, HIV viral load in ZNS, HIV viral load in genital, Lumbar puncture and HIV viral load in ZNS, Monotherapy and compartment failure (ZNS and genital), ZNS viral load under monotherapy, Genital viral load under monotherapy, Neuropsychological tests (HIV Dementia), Treatment Experienced
- Medical subject headings
- HIV Infections, AIDS Dementia Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lopinavir-MonotherapyDrug
Also called Kaletra
Patients on triple HAART will be switched to LPV/r-monotherapy
HAARTDrug
Also called Any ART
Patients will continued their current HAART
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy | Experimental | Ritonavir-boosted lopinavir (Kaletra®) will be used as monotherapy Receives: Drug: Lopinavir-Monotherapy |
| Continued ART | Active comparator | Continuation Therapy, conventional triple HAART Receives: Drug: HAART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Failure in CNS
Measured: Week 48
Secondary outcomes (1)
Predictors of failure
Measured: week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2007 (estimated)
- Study startJan 2007
- Primary completionSep 2008
- Study completionDec 2008
Why it stopped: Unexpectedely high rates of treatment-failure
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 InfectionsStudies 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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cantonal Hospital of St. Gallen
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Swiss HIV Cohort Study
- Responsible party
- Principal investigator, pietro vernazza, Cantonal Hospital of St. Gallen
- Investigators
- Pietro Vernazza, Professor, Principal investigator, Swiss HIV Cohort Study
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00531986
- Sponsor's protocol ID
- SHCS-Projekt Nr.: 490
- Other IDs
- SHCS 490
- Acronym
- MOST
- Status last verified
- Jul 2018
- First submitted
- 18 Sep 2007
- Last updated
- 18 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gutmann C, Cusini A, Gunthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly S, Vernazza PL; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS. 2010 Sep 24;24(15):2347-54. doi: 10.1097/QAD.0b013e32833db9a1.
PubMed 20802298
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HIV- Monotherapy in Switzerland (MOST- ch)
- ClinicalTrials.gov ID
- NCT00531986
- Acronym / sponsor ID
- MOST / SHCS-Projekt Nr.: 490
- Conditions
- HIV Infections
- Keywords
- Monotherapy, Neuropsychological tests, HIV viral load in ZNS, HIV viral load in genital, Lumbar puncture and HIV viral load in ZNS, Monotherapy and compartment failure (ZNS and genital), ZNS viral load under monotherapy, Genital viral load under monotherapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unexpectedely high rates of treatment-failure
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Cantonal Hospital of St. GallenUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, Swiss HIV Cohort Study
- Study start
- Jan 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 19 Sep 2007 (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 investigators plan to conduct a two arm study, to compare failure rates in the central nervous system (CNS) and genital compartment in virologically fully suppressed patients continuing a highly active antiretroviral therapy (HAART) versus patients switching to ritonavir boosted lopinavir (Kaletra®) HIV-monotherapy. The study is composed of two phases of 48 weeks duration.
In addition, neuropsychological tests (Color trial test A 1 and 2; Grooved pegboard; EWIA Digit Symbol form) and evaluation of side effects will be performed.
Detailed description
In the first phase (phase A), ritonavir-boosted lopinavir (Kaletra®) will be compared with continued HAART. In the second year (phase B) patients on conventional HAART are also offered LPV/r monotherapy to extend the longterm experience of this new strategy.
Only patients willing to give a genital secretion and a spinal fluid sample will be included. All patients must be on a fully suppressive HAART with at least 2 consecutive values of HIV-RNA at the screening visit . After performance of lumbar puncture at baseline, patients will be randomized to continued HAART or LPV/r monotherapy. During the first year of randomized treatment patients will be followed at week 6/ 12 /18 /24 /32 /40 and 48. Lumbar puncture and genital secretion sampling will be repeated at week 48.
Follow up during the second phase (B: W48-96) of the study will be identical to phase A including genital and spinal sampling at week 96. After study termination at week 96, patients may opt to continue monotherapy if results of HIV-RNA in blood and CSF support this decision.
The primary endpoint of the study will be treatment failure in the compartment (CSF and / or genital tract). Since the variability of HIV-RNA determination in CSF and genital secretions is not very well known, a one log increase above the baseline value will be considered as treatment failure in the respective compartment. Only patients who had a complete viral suppression in blood will be considered for compartment evaluation. Patients treated in the monotherapy arm with a CSF HIV-RNA value at week 48 more than 1.0 log10 cp/ml above baseline (= compartment failure) will be switched to a conventional combination treatment. HIV-RNA testing in the genital samples will be performed batchwise at the end of the study.
In addition, patients with a blood treatment failure (two consecutive HIV-RNA detections > 400cp/ml) will be considered as full treatment failures and switched to a rescue regimen at the discretion of the treating physician. For the analysis, these patients will be considered as systemic treatment failure and will not be entered in the analysis of compartmentalized treatment failure. If the rescue strategy was only intensification of adherence and results in full blood viral load re-suppression, the patient will still be maintained in the study and compartment evaluations can be performed at w48 and/or 96, respectively.
The secondary aim of the study is the definition of prognostic markers for compartment failures. Potential risk factors associated with mono-maintenance failure are HIV-DNA load at time of treatment simplification, HIV-RNA at the time of first treatment initiation, duration of HIV-RNA suppression before simplification, history of HIV-RNA blips, presence of detectable HIV-RNA in spinal fluid at the time of treatment simplification, changes of level of c-reactive protein (high sensitive methodology, hsCRP) from baseline as a marker of immune-activation during the maintenance therapy.
If funding allows, we will test for the presence of resistant viruses and compare the presence of genetic polymorphism at baseline. We will also measure parameters of immunoactivation (hsCRP, CD8+, CD38+).
The study is financed by the Swiss National Science Foundation and the Swiss HIV Cohort Study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Monotherapy | Experimental | Drug: Lopinavir-MonotherapyRitonavir-boosted lopinavir (Kaletra®) will be used as monotherapy |
| Continued ART | Active comparator | Drug: HAARTContinuation Therapy, conventional triple HAART |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age > 18 years.
- HIV seropositive.
- HAART (> 6 months) with at least 3 months successfully suppressed HIV- RNA (two most recent RNA measurements < 50 cp/ml). HAART is defined as either:
- HIV-RNA in plasma < 50 cp/ml at screening.
- Stable antiretroviral therapy (unchanged drug combination) during the last four weeks.
Key exclusion criteria (7 listed)
- Other investigational substance or substances active against HIV.
- Previous history of adverse events with the drugs under investigation.
- Previous history of any virological treatment failure (does not include deliberate treatment interruption) or documented resistance against the drugs under investigation (LPV/r).
- Patient who has no effective alternative treatment options in case the study treatment fails (according to the physician's judgment).
- Pregnancy (negative pregnancy test for women of childbearing potential at screening).
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 |
|---|---|---|
| Lopinavir-MonotherapyAlso: KaletraPatients on triple HAART will be switched to LPV/r-monotherapy | Drug | Monotherapy |
| HAARTAlso: Any ARTPatients will continued their current HAART | Drug | Continued ART |
Primary outcome
Failure in CNS
Time frame: Week 48
1 secondary outcome
Predictors of failure
Time frame: week 48
Results and safety
The study was stopped early (reason given: Unexpectedely high rates of treatment-failure). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
- Derived from this study: PubMed 20802298Gutmann C, Cusini A, Gunthard HF, Fux C, Hirschel B, Decosterd LA, Cavassini M, Yerly S, Vernazza PL; Swiss HIV Cohort Study (SHCS). Randomized controlled study demonstrating failure of LPV/r monotherapy in HIV: the role of compartment and CD4-nadir. AIDS. 2010 Sep 24;24(15):2347-54. doi: 10.1097/QAD.0b013e32833db9a1.
- Related InfoLink provided by the sponsor.
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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.
Pietro Vernazza, Professor principal investigator
Swiss HIV Cohort Study
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lopinavir-Monotherapy and HAART in people with HIV Infections, run by Cantonal Hospital of St. Gallen at 6 sites in Switzerland.
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 11 inclusion and 7 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: stopped early, as of the sponsor's last update on 18 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study was stopped early (reason given: Unexpectedely high rates of treatment-failure). 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?
Failure in CNS (time frame: Week 48). 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 NCT00531986, 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 18 Jul 2018.