HIV InfectionsPhase 3NCT00440271
SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
A Phase 3 study testing tipranavir, ritonavir and Optimized Background Regimen (OBR) in people with HIV Infections, run by Boehringer Ingelheim at 30 sites in 7 countries.
Trial summary
The primary purpose of this study is to: 1. Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially diverse HIV+ population (males and females) who are three-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease… 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?
- tipranavir, ritonavir and Optimized Background Regimen (OBR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 30 sitesin 7 countries
- Study dates
- Feb 2007to Oct 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Main inclusion criteria for the study are:
- HIV-1 infected adults, men and women at least 18 years of age.
- 3-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) treatment-experienced (min of 3-months duration for each class) with resistance to more than one PI (on screening resistance testing). NNRTI-naïve patients who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible.
- CD4+ T lymphocyte count >=50 cells/mm3.
- HIV-1 viral load >=1,000 copies/mL at screening.
- The antiretroviral (ARV) study treatment regimen must consist of TPV/r in combo with an optimized background regimen (OBR) of 2-4 agents: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, a trial approved expanded access program (EAP) investigational agent.
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- Acceptable screening laboratory values that indicate adequate baseline organ function.
- Acceptable medical history with a chest X-ray without evidence of active disease and an electrocardiogram (ECG) without clinically important abnormalities within one year of the study.
- A reliable method of barrier contraception will be used by all female patients who are of childbearing potential.
Who cannot join
- Main exclusion criteria for the study are:
- Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
- ARV medication naïve.
- Genotypic resistance to TPV (defined as a TPV mutation score >7).
- Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
- Prior tipranavir use.
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- Inability to adhere to the requirements of the protocol.
- Patients with prior history of hemorrhagic stroke or intracranial aneurysm.
- Patients with a history of ischemic stroke, neurosurgery or skull trauma within 4 weeks prior to screening.
- History of Progressive Multifocal Leukoencephalopathy, Visceral Kaposi's Sarcoma, and/or any malignancy.
- Any acquired immunodeficiency syndrome (AIDS) defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit.
Trial locations and contacts
30 sites in 7 countries.
30 sites in 7 countries
United States16 sites
1182.98.006 Boehringer Ingelheim Investigational Site
Akron, Ohio
1182.98.023 Boehringer Ingelheim Investigational Site
Austin, Texas
1182.98.007 Boehringer Ingelheim Investigational Site
Cincinnati, Ohio
1182.98.018 Boehringer Ingelheim Investigational Site
Clearwater, Florida
1182.98.004 Boehringer Ingelheim Investigational Site
Decatur, Georgia
1182.98.014 Boehringer Ingelheim Investigational Site
Fort Lauderdale, Florida
1182.98.009 Boehringer Ingelheim Investigational Site
Houston, Texas
1182.98.040 Boehringer Ingelheim Investigational Site
Huntersville, North Carolina
1182.98.002 Boehringer Ingelheim Investigational Site
Kansas City, Missouri
1182.98.016 Boehringer Ingelheim Investigational Site
New York, New York
1182.98.026 Boehringer Ingelheim Investigational Site
New York, New York
1182.98.020 Boehringer Ingelheim Investigational Site
Oklahoma City, Oklahoma
1182.98.041 Boehringer Ingelheim Investigational Site
Orlando, Florida
1182.98.029 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1182.98.034 Boehringer Ingelheim Investigational Site
Stony Brook, New York
1182.98.033 Boehringer Ingelheim Investigational Site
Washington D.C., District of Columbia
Brazil4 sites
1182.98.55002 Hospital DIA
Sacomã - São Paulo
1182.98.55004 Unidade de Referência em doenças Infecciosas Preveníveis
Santo André
1182.98.55001 Universidade Federal de Sao Paulo
São Paulo
1182.98.55003 Centro de Referência e Treinamento - DST/AIDS
Vila Mariana - Sao Paulo
Argentina3 sites
1182.98.5405 CENTRO de INFECTOLOGIA y ASISTENCIA (CIAS)
Capital Federal ,Buenos Aires
1182.98.5403 Centro Hospital Higa - Dr Oscar Alende
Mar del Plata
1182.98.5402 Caici
Rosario
Germany2 sites
1182.98.4903 Boehringer Ingelheim Investigational Site
Bochum
1182.98.4908 Boehringer Ingelheim Investigational Site
Hamburg
Canada1 site
1182.98.1007 Boehringer Ingelheim Investigational Site
Quebec, Ste Foy, Quebec
About this study
Official title: SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavi/r IN Race/Gender HIV+ Patients Randomized to Therapeutic Drug Monitoring or Standard of Care
The primary purpose of this study is to:
- Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially diverse HIV+ population (males and females) who are three-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) experienced with documented resistance to more than one PI.
- Determine pharmacokinetic data in this racially and gender diverse population.
- Determine the potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.
- Conditions
- HIV Infections
- Being tested
- tipranavir, ritonavir, Optimized Background Regimen (OBR)
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tipranavirDrug
ritonavirDrug
Optimized Background Regimen (OBR)Drug
Also called Nucleoside Reverse Transcriptase Inhibitors (NRTIs),, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),, Enfuvirtide,, Maraviroc,
Patients received between two and four active anti-retroviral medications based on resistance testing results, as background treatment, and remained on these for the duration of the trial.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (SoC) | Other | Standard of Care (SOC) Arm = Tipranavir/ritonavir (TPV/r) capsules taken orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR). No TPV/r dose changes were permitted. Receives: Drug: tipranavir; Drug: ritonavir; Drug: Optimized Background Regimen (OBR) |
| Therapeutic Drug Monitoring (TDM) | Other | Therapeutic Drug Monitoring (TDM) Arm = Patients began by receiving standard of care (SOC) tipranavir/ritonavir (TPV/r) capsules orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR) followed, if needed, by TPV or ritonavir (RTV) dose adjustments at Week 4, 6, 10, 14, 18, 22, 26 and 30 based on viral response, phenotypic inhibitory quotient (IQ), and TPV trough concentrations. Receives: Drug: tipranavir; Drug: ritonavir; Drug: Optimized Background Regimen (OBR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Response at Week 48
percentage of participants whose viral load <50 copies/mL at Week 48
Measured: after 48 weeks of treatment
Secondary outcomes (13)
Percentage of Participants Whose Viral Load <50 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Percentage of Participants Whose ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Change in Viral Load From Baseline at Each Visit
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Time to Treatment Failure
For patients who never achieve a confirmed virologic response, time to treatment failure is defined as 0. For patients who achieve a confirmed virologic response, time to treatment failure is the earliest time of either: death, permanent discontinuation of the study drug or loss to follow-up, introduction of a new anti-retroviral drug to the regimen if it is not solely related to either toxicity or intolerance clearly attributable to a background drug, but not the study drug, or first occurrence of a VL >50 copies/mL at two consecutive measurements after having achieved a VL <50 copies/mL.
Measured: after Day 1 of treatment
Time to New AIDS or AIDS Related Progression Event or Death
Measured: after Day 1 of treatment
Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48
Measured: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Measured: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Measured: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Patients Adherence With Study Medication Based on Pill Count
Measured: after 4 weeks of treatment
Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Occurrence of TPV Trough Concentration >120 μM
Measured: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Post-dose TPV and RTV Concentrations at Week 4
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionOct 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00440271
- Sponsor's protocol ID
- 1182.98
- Other IDs
- EudraCT No.: 2005-005264-86
- Status last verified
- Jan 2014
- First submitted
- 26 Feb 2007
- Last updated
- 27 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavi/r IN Race/Gender HIV+ Patients Randomized to Therapeutic Drug Monitoring or Standard of Care
- ClinicalTrials.gov ID
- NCT00440271
- Acronym / sponsor ID
- 1182.98
- Conditions
- HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Oct 2008 (actual)
- First posted
- 27 Feb 2007 (estimated)
- Results
- Posted 26 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to:
- Demonstrate the safety and efficacy of tipranavir/ritonavir (TPV/r) among a racially diverse HIV+ population (males and females) who are three-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) experienced with documented resistance to more than one PI.
- Determine pharmacokinetic data in this racially and gender diverse population.
- Determine the potential utility of using therapeutic drug monitoring (TDM) in improving efficacy outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (SoC) | Other | Drug: tipranavir, Drug: ritonavir, Drug: Optimized Background Regimen (OBR)Standard of Care (SOC) Arm = Tipranavir/ritonavir (TPV/r) capsules taken orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR). No TPV/r dose changes were permitted. |
| Therapeutic Drug Monitoring (TDM) | Other | Drug: tipranavir, Drug: ritonavir, Drug: Optimized Background Regimen (OBR)Therapeutic Drug Monitoring (TDM) Arm = Patients began by receiving standard of care (SOC) tipranavir/ritonavir (TPV/r) capsules orally at a dose of 500 mg/200 mg twice a day (BID) plus optimized background regimen (OBR) followed, if needed, by TPV or ritonavir (RTV) dose adjustments at Week 4, 6, 10, 14, 18, 22, 26 and 30 based on viral response, phenotypic inhibitory quotient (IQ), and TPV trough concentrations. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- HIV-1 infected adults, men and women at least 18 years of age.
- 3-class (nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI)) treatment-experienced (min of 3-months duration for each class) with resistance to more than one PI (on screening resistance testing). NNRTI-naïve patients who have genotypically documented NNRTI-resistance mutations on past or screening resistance testing would be eligible.
- CD4+ T lymphocyte count >=50 cells/mm3.
- HIV-1 viral load >=1,000 copies/mL at screening.
- The antiretroviral (ARV) study treatment regimen must consist of TPV/r in combo with an optimized background regimen (OBR) of 2-4 agents: N(t)RTIs (NRTI or NtRTI), enfuvirtide (ENF), and/or, where available, a trial approved expanded access program (EAP) investigational agent.
Key exclusion criteria (11 listed)
- Known hypersensitivity to the tipranavir (TPV) or ritonavir (RTV).
- ARV medication naïve.
- Genotypic resistance to TPV (defined as a TPV mutation score >7).
- Patients on recent drug holiday, defined as off antiretroviral (ARV) medications for at least 7 consecutive days within the month prior to screening.
- Prior tipranavir use.
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 |
|---|---|---|
| tipranavir | Drug | Standard of Care (SoC), Therapeutic Drug Monitoring (TDM) |
| ritonavir | Drug | Standard of Care (SoC), Therapeutic Drug Monitoring (TDM) |
| Optimized Background Regimen (OBR)Also: Nucleoside Reverse Transcriptase Inhibitors (NRTIs),, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs),, Enfuvirtide,, Maraviroc,Patients received between two and four active anti-retroviral medications based on resistance testing results, as background treatment, and remained on these for the duration of the trial. | Drug | Standard of Care (SoC), Therapeutic Drug Monitoring (TDM) |
Primary outcome
Treatment Response at Week 48
Time frame: after 48 weeks of treatment
percentage of participants whose viral load <50 copies/mL at Week 48
13 secondary outcomes
Percentage of Participants Whose Viral Load <50 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Percentage of Participants Whose Viral Load <400 Copies/mL at Each Visit Including Visits at Weeks 24 and 48
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Percentage of Participants Whose ≥1 log10 Drop in Viral Load From Baseline at All Visits, Including Visits at Weeks 24 and 48
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Change in Viral Load From Baseline at Each Visit
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Time to Treatment Failure
Time frame: after Day 1 of treatment
Time to New AIDS or AIDS Related Progression Event or Death
Time frame: after Day 1 of treatment
Change in CD4+ and CD8+ Cell Counts From Baseline at Each Visit Including Visits at Week 24 and Week 48
Time frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Change in Ratio of CD38+/CD8+ From Baseline to Week 48
Time frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Tipranavir (TPV) and Ritonavir (RTV) Trough Concentrations at Week 2, Week 4, Week 8, Week 12, Week 24, Week 36 and Week 48
Time frame: after 2 weeks of treatment till Week 48 (Weeks 2, 4, 8, 12, 24, 36, and 48)
Patients Adherence With Study Medication Based on Pill Count
Time frame: after 4 weeks of treatment
Occurrence of TPV Inhibitory Quotient (IQ) >60 at Each Visit Where TPV Concentration is Measured
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Occurrence of TPV Trough Concentration >120 μM
Time frame: after 2 weeks of treatment (Weeks 2, 4, 8, 12, 24, 36, and 48)
Post-dose TPV and RTV Concentrations at Week 4
Time frame: Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Boehringer Ingelheim study chair
Boehringer Ingelheim
30 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tipranavir, ritonavir and Optimized Background Regimen (OBR) in people with HIV Infections, run by Boehringer Ingelheim at 30 sites in 7 countries.
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 9 inclusion and 11 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 27 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Brazil, Argentina, Spain, Germany and 2 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Treatment Response at Week 48 (time frame: after 48 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2014.