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HIVPhase 4NCT00342355

Antiretroviral Therapy for Advanced HIV Disease in South Africa

A Phase 4 study testing Zidovudine, Stavudine and Didanosine in people with HIV, run by National Institutes of Health Clinical Center (CC) at 7 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will determine how well four different antiretroviral drug therapies work in patients with advanced HIV disease. The trial is part of the South Africa-U.S. Project Phidisa Programme - a collaboration between the South African Military Health Service (SAMHS) of the South African National Defense Force… Read more about this study

Who is it for?
Ages 14 years and older
Conditions the study is for
HIV
What is being tested?
Zidovudine, Stavudine and Didanosine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,771 participants
Where
7 sitesSouth Africa
Study dates
Jan 2004to Aug 2008
Phase
Phase 4
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 14 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Uniformed SANDF personnel or family members of SANDF personnel who are registered as eligible for health services from the SAMHS.
  • HIV positive as diagnosed and/or confirmed in PHIDISA I OR documented HIV infection from an accredited source.
  • CD4+ cell count less than 200 cells/microL (or less than or equal to 14% for patients post-splenectomy) AND/OR any AIDS defining illness currently or historically. Patients with pulmonary tuberculosis must have a CD4+ cell count less than 200 cells/microL. Patients with KS must have a CD4+ cell count less than 200 cells/microL unless their sarcoma is progressive and/or requires chemotherapy.
  • Antiretroviral treatment naive (less than 7 days cumulative exposure to any antiretroviral drug) or treated for post-exposure prophylaxis without becoming HIV infected at that time.
  • Laboratory variables as follows:
  • Haemoglobin greater than or equal to 9.0g/dL for men and greater than or equal to 8.0g/dL for women.
Show all 13Show fewer
  • Absolute neutrophil count greater than or equal to 500 cells/microL.
  • Platelet count greater than or equal to 25,000/mm(3).
  • Serum transaminase (ALT or AST) less than or equal to 5 times upper limit of normal (ULN).
  • 14 years or older.
  • Likely to be compliant with study procedures and clinical visits in the opinion of the clinical investigator (guidance is provided in the protocol to assist clinicians in making this decision).
  • Have completed the PHIDISA treatment adherence counseling session.
  • Provision of written informed consent.

Who cannot join

  • Any history of pancreatitis or serious pathology indicative of increased risk for pancreatitis.
  • Current requirement for use of a medication that is contra-indicated with the PHIDISA II study drugs. Where possible, alternate therapies should be selected in order to facilitate randomization. Patients entering the study with tuberculosis should defer screening and randomization until successful completion of an induction course of anti-mycobacterium therapy including rifampicin. As appropriate this patient could recommence screening when starting the maintenance regimen of anti-tubercular drugs excluding rifampicin.
  • Pregnancy (following delivery, such women may be enrolled).

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

South Africa7 sites

  • South African Military Health Services (SAMHS)

    Centurion

  • Umtata Sickbay

    Eastaern Cape

  • 3 Military Hospital

    Free State

  • 1 Military Hospital

    Gauteng

  • Mtubatuba SIckbay

    Kwazulu-Natal

  • Phalaborwa Sickbay

    Limpopo

  • 2 Military Hospital

    Western Cape

Other trials in South Africa

About this study

Official title: Randomized, Open-Label 2x2 Factorial Study to Compare the Safety and Efficacy of Different Combination Antiretroviral Therapy Regimens in Treatment Naive Patients With Advanced HIV Disease and/or CD4+ Cell Counts Less Than 200 Cells/MicroL

This study will determine how well four different antiretroviral drug therapies work in patients with advanced HIV disease. The trial is part of the South Africa-U.S. Project Phidisa Programme - a collaboration between the South African Military Health Service (SAMHS) of the South African National Defense Force (SANDF), the U.S. Department of Defense, and the U.S. National Institutes of Health - to help prevent HIV transmission among South African military and civilian employees and their families.

Members of the SANDF with HIV infection may be eligible for this study. HIV-infected family members who are 14 years of age and older may also participate. All participants must have a CD4 count of less than 200 or an AIDS-defining illness.

Read more

Participants are randomly assigned to one of the following four antiretroviral drug regimens, which require taking 5 pills or more every day:

  • AZT (zidovudine) + ddl (didanosine) + EFV (efavirenz)
  • AZT (zidovudine) + ddl (didanosine) + r/LPV (lopinavir/ritonavir)
  • D4T (stavudine) + 3TC (lamivudine) + EFV (efavirenz)
  • D4T (stavudine) + 3TC (lamivudine) + r/LPV (lopinavir/ritonavir)

Patients are followed for up to 6 years. Clinic visits are scheduled once a month for the first 3 months and then once every 3 months for the next five years. Patients undergo a medical history, physical examination, and blood tests at each visit, and complete questionnaires of behavior, quality of life, and force readiness every year.

Read the detailed description

This is a randomized, open label 2x2 factorial study of four regimens of initial therapy.

  1. AZT + ddl + EFV

II. AZT + ddl + r/LPV

III. D4T + 3TC + EFV

IV. D4T + 3TC + r/LPV

Eligible patients will commence their randomly allocated study drugs as soon as possible after randomization. Episodes of treatment limiting toxicity will be managed in keeping with protocol specified guidelines.

Patients who experience treatment failures (as specified in the protocol) will be managed by changing their regimen to that corresponding to one of the other treatment groups.

Conditions
HIV
Being tested
Zidovudine, Stavudine, Didanosine, Lamivudine, Efavirenz
Keywords
Protease Inhibitors, Reverse Transcriptase Inhibitors, AIDS, Opportunistic Infections, Resource-Poor
Medical subject headings
Acquired Immunodeficiency Syndrome, Opportunistic Infections

What participants receive

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

  • ZidovudineDrug

    Also called AZT

    600 mg once daily

  • StavudineDrug

    Also called D4T

    40 mg once daily

  • DidanosineDrug

    Also called DDI

    <60 kg/125 mg twice daily or >60kg/200 mg twice daily

  • LamivudineDrug

    Also called 3TC

    300 mg once daily

  • EfavirenzDrug

    Also called EFV

    600 mg once daily

  • Lopinavir/RitonavirDrug

    Also called Kaletra

    r/LPV 400mg/100mg twice daily

Study groups in NCT00342355
Study groupRoleWhat they receive
AZT+DDI+EFVActive comparatorZidovudine,Didanosine,Efavirenz ( Zidovudine 600 mg once daily,Didanosine <60 kg/125 mg twice daily or >60kg/200 mg twice daily,Efavirenz 600 mg once daily)
Receives: Drug: Zidovudine; Drug: Didanosine; Drug: Efavirenz
AZT+DDI+r/LPVActive comparatorZidovudine,Didanosine,Lopinavir/Ritonavir(AZT 600 mg once daily,DDI 100 mg twice daily,r/LPV 400mg/100mg twice daily)
Receives: Drug: Zidovudine; Drug: Didanosine; Drug: Lopinavir/Ritonavir
d4T+3TC+EFVActive comparatorStavudine,Lamivudine,Efavirenz(d4T 40 mg twice daily,3TC 300 mg once daily,EFV 600 mg once daily)
Receives: Drug: Stavudine; Drug: Lamivudine; Drug: Efavirenz
d4T+3TC+r/LPVActive comparatorStavudine,Lamivudine,Lopinavir/Ritonavir(d4T 40m mg twice daily,3TC 300 mg once daily,r/LPV 400mg/100mg twice daily)
Receives: Drug: Stavudine; Drug: Lamivudine; Drug: Lopinavir/Ritonavir

What is being measured

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

  1. Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens.

    Progression of disease, AIDS, or death in treatment naive patients with advanced HIV diagnosis will be evaluated in the four randomly assigned regimens.

    Measured: January 2004 until March 31 2008

Secondary outcomes (1)

  1. Serious Adverse Events

    Safety outcomes in four different randomly assigned regimens

    Measured: January 2004 until March 31, 2008

Timeline

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

  1. First posted21 Jun 2006 (estimated)
  2. Study startJan 2004
  3. Primary completionMar 2008
  4. Study completionAug 2008

Resources

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
Factorial
Masking
None (open label)
Enrolment
1,771 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00342355
Sponsor's protocol ID
999904094
Other IDs
04-I-N094
Status last verified
Apr 2013
First submitted
19 Jun 2006
Last updated
21 May 2013
Data monitoring committee
Yes

Publications

  • Rabkin M, El-Sadr W, Katzenstein DA, Mukherjee J, Masur H, Mugyenyi P, Munderi P, Darbyshire J. Antiretroviral treatment in resource-poor settings: clinical research priorities. Lancet. 2002 Nov 9;360(9344):1503-5. doi: 10.1016/S0140-6736(02)11478-4. No abstract available.

    PubMed 12433534

  • Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ Jr, Feinberg JE, Balfour HH Jr, Deyton LR, Chodakewitz JA, Fischl MA. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997 Sep 11;337(11):725-33. doi: 10.1056/NEJM199709113371101.

    PubMed 9287227

  • Cameron DW, Heath-Chiozzi M, Danner S, Cohen C, Kravcik S, Maurath C, Sun E, Henry D, Rode R, Potthoff A, Leonard J. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group. Lancet. 1998 Feb 21;351(9102):543-9. doi: 10.1016/s0140-6736(97)04161-5.

    PubMed 9492772

  • Ledwaba L, Tavel JA, Khabo P, Maja P, Qin J, Sangweni P, Liu X, Follmann D, Metcalf JA, Orsega S, Baseler B, Neaton JD, Lane HC; Project Phidisa Biomarkers Team. Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS One. 2012;7(3):e24243. doi: 10.1371/journal.pone.0024243. Epub 2012 Mar 20.

    PubMed 22448211

  • Matthews GV, Manzini P, Hu Z, Khabo P, Maja P, Matchaba G, Sangweni P, Metcalf J, Pool N, Orsega S, Emery S; PHIDISA II study team. Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa. AIDS. 2011 Sep 10;25(14):1727-35. doi: 10.1097/QAD.0b013e328349bbf3.

    PubMed 21716078

  • Phidisa II Writing Team for Project Phidisa; Ratsela A, Polis M, Dhlomo S, Emery S, Grandits G, Khabo P, Khanyile T, Komati S, Neaton JD, Naidoo LC, Magongoa D, Qolohle D. A randomized factorial trial comparing 4 treatment regimens in treatment-naive HIV-infected persons with AIDS and/or a CD4 cell count <200 cells/muL in South Africa. J Infect Dis. 2010 Nov 15;202(10):1529-37. doi: 10.1086/656718. Epub 2010 Oct 13.

    PubMed 20942650

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Zidovudine, Stavudine and Didanosine in people with HIV, run by National Institutes of Health Clinical Center (CC) at 7 sites in South Africa.

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 13 inclusion and 3 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: finished, as of the sponsor's last update on 21 May 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in South Africa. 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?

Yes. Results are posted in the registry (first posted 16 Apr 2013). 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?

Progression to AIDS or Death in tx naïve Pts With Adv HIV dx in the Four Randomly Assigned Regimens. (time frame: January 2004 until March 31 2008). 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 NCT00342355, which also lists 6 linked publications.

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 May 2013.

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