HIVPhase 3NCT00745823

A Study to Determine the Safety and Efficacy of Once Daily Raltegravir Compared to Twice Daily Raltegravir (MK-0518-071)

A Phase 3 study testing Comparator: Raltegravir 400 mg b.i.d., Experimental: Raltegravir 800 mg q.d. and TRUVADA™ in people with HIV, run by Merck Sharp & Dohme LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

A study to evaluate the safety, tolerability and efficacy of once daily Raltegravir compared to twice daily raltegravir when each is given in combination with TRUVADA™ in treatment-naïve human immunodeficiency virus (HIV)-infected patients. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV
What is being tested?: Comparator: Raltegravir 400 mg b.i.d., Experimental: Raltegravir 800 mg q.d. and TRUVADA™
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 775 participants
Where: No sites listed yet
Study dates: Sep 2008to May 2011
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

Patient is male or female 18 years of age or older
Patient is HIV positive
Patient is naïve to antiretroviral therapy (ART) or has received less than 7 days total of any ART
Extension Study:
The planned extension study did not take place as the study was terminated after the Week 48 analysis.

Who cannot join

Patient is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence
Patient has documented resistance to tenofovir or emtricitabine
Patient is currently participating or has participated in a study with an investigational compound or device within 45 days of signing informed consent
Patient is pregnant or breastfeeding, or expecting to conceive

About this study

Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of Once Daily Raltegravir (MK0518) Versus Twice Daily Raltegravir, Each in Combination With TRUVADA™, in Treatment-Naïve HIV Infected Patients

Read the detailed description

Following the 96-week double-blind study period (MK0518-071)(NCT00745823), subjects may enroll in an extension study (MK0518-071-10)(NCT00745823). From weeks 96 to 120, subjects' treatment assignments will remain as in the base study.

From week 120 to 240, all subjects will receive open-label raltegravir (800 mg, once daily) in combination with TRUVADA™.

Conditions: HIV
Being tested: Comparator: Raltegravir 400 mg b.i.d., Experimental: Raltegravir 800 mg q.d., TRUVADA™
Keywords: HIV Infections, Treatment Naïve
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Comparator: Raltegravir 400 mg b.i.d.Drug
Also called ISENTRESS™
Raltegravir 400 mg tablet by mouth (PO) twice daily (b.i.d.) + two raltegravir placebo tablets + one tablet of TRUVADA™ once daily (q.d.)
Experimental: Raltegravir 800 mg q.d.Drug
Also called ISENTRESS™
Raltegravir 800 mg tablet PO q.d. + two raltegravir placebo tablets + one tablet TRUVADA™ q.d.
TRUVADA™Drug
One tablet TRUVADA™ q.d. (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate)

Study groups in NCT00745823
Study group	Role	What they receive
Raltegravir 400 mg b.i.d.	Active comparator	Not described Receives: Drug: Comparator: Raltegravir 400 mg b.i.d.; Drug: TRUVADA™
Raltegravir 800 mg q.d.	Experimental	Not described Receives: Drug: Experimental: Raltegravir 800 mg q.d.; Drug: TRUVADA™

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks
Measured: Week 48
Number of Participants With One or More Adverse Events at 48 Weeks
Measured: Week 48
Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks
Measured: Week 48

Secondary outcomes (7)

Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks
Measured: 48 weeks
Mean Change From Baseline to Week 48 in CD4 Cell Count
Measured: Baseline and Week 48
Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Measured: Week 96
Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Measured: Week 96
Mean Change From Baseline to Week 96 in CD4 Cell Count
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Measured: Baseline and Week 96
Number of Participants With One or More Adverse Events at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Measured: Week 96
Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks
As the study was terminated after the 48-week analysis, the planned secondary analyses for Week 96 were not performed.
Measured: Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008May 2011

First posted3 Sep 2008 (estimated)
Study startSep 2008
Primary completionOct 2010
Study completionMay 2011

Why it stopped: Primary efficacy analysis at Week 48 did not demonstrate non-inferiority of raltegravir 800 mg once daily versus raltegravir 400 mg twice daily

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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: Double blind
Who is masked: Participant, Investigator
Enrolment: 775 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00745823
Sponsor's protocol ID: 0518-071
Other IDs: 2008_543, CTRI/2009/091/000145
Status last verified: Feb 2017
First submitted: 2 Sep 2008
Last updated: 21 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG, Young B, Katlama C, Gatell-Artigas JM, Arribas JR, Nelson M, Campbell H, Zhao J, Rodgers AJ, Rizk ML, Wenning L, Miller MD, Hazuda D, DiNubile MJ, Leavitt R, Isaacs R, Robertson MN, Sklar P, Nguyen BY; QDMRK Investigators. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis. 2011 Dec;11(12):907-15. doi: 10.1016/S1473-3099(11)70196-7. Epub 2011 Sep 18.
PubMed 21933752

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Study the Safety and Efficacy of Once Daily Raltegravir (MK0518) Versus Twice Daily Raltegravir, Each in Combination With TRUVADA™, in Treatment-Naïve HIV Infected Patients
ClinicalTrials.gov ID: NCT00745823
Acronym / sponsor ID: 0518-071
Conditions: HIV
Keywords: HIV Infections, Treatment Naïve
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Primary efficacy analysis at Week 48 did not demonstrate non-inferiority of raltegravir 800 mg once daily versus raltegravir 400 mg twice daily
Enrolment: 775 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Sep 2008
Primary completion: Oct 2010 (actual)
Study completion: May 2011 (actual)
First posted: 3 Sep 2008 (estimated)
Results: Posted 25 Apr 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

From week 120 to 240, all subjects will receive open-label raltegravir (800 mg, once daily) in combination with TRUVADA™.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Raltegravir 400 mg b.i.d.	Active comparator	Drug: Comparator: Raltegravir 400 mg b.i.d., Drug: TRUVADA™
Raltegravir 800 mg q.d.	Experimental	Drug: Experimental: Raltegravir 800 mg q.d., Drug: TRUVADA™

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patient is male or female 18 years of age or older
Patient is HIV positive
Patient is naïve to antiretroviral therapy (ART) or has received less than 7 days total of any ART
The planned extension study did not take place as the study was terminated after the Week 48 analysis.

Key exclusion criteria (4 listed)

Patient is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence
Patient has documented resistance to tenofovir or emtricitabine
Patient is currently participating or has participated in a study with an investigational compound or device within 45 days of signing informed consent
Patient is pregnant or breastfeeding, or expecting to conceive

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
Comparator: Raltegravir 400 mg b.i.d.Also: ISENTRESS™Raltegravir 400 mg tablet by mouth (PO) twice daily (b.i.d.) + two raltegravir placebo tablets + one tablet of TRUVADA™ once daily (q.d.)	Drug	Raltegravir 400 mg b.i.d.
Experimental: Raltegravir 800 mg q.d.Also: ISENTRESS™Raltegravir 800 mg tablet PO q.d. + two raltegravir placebo tablets + one tablet TRUVADA™ q.d.	Drug	Raltegravir 800 mg q.d.
TRUVADA™One tablet TRUVADA™ q.d. (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate)	Drug	Raltegravir 400 mg b.i.d., Raltegravir 800 mg q.d.

Primary outcome

Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks
Time frame: Week 48
Number of Participants With One or More Adverse Events at 48 Weeks
Time frame: Week 48
Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks
Time frame: Week 48

7 secondary outcomes

Number of Participants With HIV Ribonucleic Acid (RNA) <400 Copies/mL at 48 Weeks
Time frame: 48 weeks
Mean Change From Baseline to Week 48 in CD4 Cell Count
Time frame: Baseline and Week 48
Number of Participants With HIV RNA <50 Copies/mL at 96 Weeks
Time frame: Week 96
Number of Participants With HIV RNA <400 Copies/mL at 96 Weeks
Time frame: Week 96
Mean Change From Baseline to Week 96 in CD4 Cell Count
Time frame: Baseline and Week 96
Number of Participants With One or More Adverse Events at 96 Weeks
Time frame: Week 96
Number of Participants Who Discontinued Due to an Adverse Event at 96 Weeks
Time frame: Week 96

Results and safety

Results posted to the registry on 25 Apr 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Raltegravir 800 mg q.d.	386	1
Raltegravir 400 mg b.i.d.	389	3

Primary outcome: Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks

Time frame: Week 48. Number. Unit: Participants

Measure	Raltegravir 800 mg q.d. n = 382	Raltegravir 400 mg b.i.d. n = 386
Value	318	343

Raltegravir 800 mg q.d. vs Raltegravir 400 mg b.i.d.: Mean Difference (Final Values): -5.7 (95% CI -10.7 to -0.83), p = 0.044, Miettinen and Nurminen

Population analysed: Data were analyzed for all participants treated with study drug. Participants who did not complete the study were treated as treatment failures.

Primary outcome: Number of Participants With One or More Adverse Events at 48 Weeks

Time frame: Week 48. Number. Unit: Participants

Measure	Raltegravir 800 mg q.d. n = 382	Raltegravir 400 mg b.i.d. n = 388
Value	331	337

Raltegravir 800 mg q.d. vs Raltegravir 400 mg b.i.d.: Mean Difference (Final Values): -0.2 (95% CI -5.0 to 4.6), Miettinen and Nurminen

Population analysed: Data were analyzed for all randomized participants who received at least one dose of study drug.

Primary outcome: Number of Participants Who Discontinued Due to an Adverse Event at 48 Weeks

Time frame: Week 48. Number. Unit: Participants

Measure	Raltegravir 800 mg q.d. n = 382	Raltegravir 400 mg b.i.d. n = 388
Value	4	3

Raltegravir 800 mg q.d. vs Raltegravir 400 mg b.i.d.: Mean Difference (Final Values): 0.3 (95% CI -1.3 to 2.0)

Population analysed: Data were analyzed for all randomized participants who received at least one dose of study drug.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Overall Study. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Raltegravir 800 mg q.d.	29 of 382 (7.6%)	287 of 382 (75.1%)	Not reported
Raltegravir 400 mg b.i.d.	46 of 388 (11.9%)	282 of 388 (72.7%)	Not reported

Limitations and caveats (from the sponsor): The study was terminated before the 96-week efficacy analysis. Adverse event data were collected for the entire treatment period up to a maximum of Week 108, which defines the Overall Study period.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 21933752Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG, Young B, Katlama C, Gatell-Artigas JM, Arribas JR, Nelson M, Campbell H, Zhao J, Rodgers AJ, Rizk ML, Wenning L, Miller MD, Hazuda D, DiNubile MJ, Leavitt R, Isaacs R, Robertson MN, Sklar P, Nguyen BY; QDMRK Investigators. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis. 2011 Dec;11(12):907-15. doi: 10.1016/S1473-3099(11)70196-7. Epub 2011 Sep 18.
Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php

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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.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Comparator: Raltegravir 400 mg b.i.d., Experimental: Raltegravir 800 mg q.d. and TRUVADA™ in people with HIV, run by Merck Sharp & Dohme LLC.

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 5 inclusion and 4 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 21 Mar 2017. 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 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 25 Apr 2012). 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?

Number of Participants With HIV Ribonucleic Acid (RNA) <50 Copies/mL at 48 Weeks (time frame: Week 48). The study lists 3 primary outcomes in all. 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 NCT00745823, 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 21 Mar 2017.