Study on the Effect of Kaletra + Nevirapine as Maintenance Bitherapy Compared to a Triple Therapy Including Kaletra + Analogues in HIV Patients

This study has been completed.
Sponsor:
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00335686
First received: June 8, 2006
Last updated: February 19, 2008
Last verified: June 2007
  Purpose

The study aims to evaluate the changes in mitochondrial DNA (mDNA) by means of the mDNA/nuclearDNA (nDNA) ratio as a marker of mitochondrial toxicity following the interruption of nucleoside analogues.


Condition Intervention Phase
HIV Infections
Drug: Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
Drug: Nevirapine (Viramune): 1 comp (200mg)/12h
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised, Prospective Multicentre Clinical Study on the Effect of the Combination of Lopinavir/Rtv + Nevirapine as Maintenance Bitherapy (Without Nucleoside Analogues) in Comparison With a Triple Therapy Including Lopinavir/Rtv + Nucleoside Analogues in HIV-Infected Patients

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit. [ Time Frame: At 24 and 48 weeks with regard to the baseline visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Study of the efficacy of the therapy with Lopinavir/rtv (3 tablets every 12 h) + Nevirapine (1 tablet every 12 h) in the maintenance of viral suppression and immune recovery in patients on HAART therapy for more than 9 months [ Time Frame: At 12, 24, 36 and 48 weeks. ] [ Designated as safety issue: No ]
  • and CV<50 copies/mL over at last 6 months [ Time Frame: At 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
  • To determine whether the combination with Lopinavir/rtv +Nevirapine is efficacious in avoiding progression to lipoatrophy/lipodystrophy or else the reversal thereof [ Time Frame: At 24 and 48 weeks ] [ Designated as safety issue: No ]
  • To study whether the combination with Lopinavir/rtv +Nevirapine makes it possible to control dyslipidemia associated with the use of Lopinavir/rtv on proving the "lipid-lowering" action of NVP [ Time Frame: At 12, 24, 36 and 48 weeks. ] [ Designated as safety issue: No ]
  • To check whether the simplified combination with the standard dose of Lopinavir/rtv with NVP is sufficient to maintain suppression of viral replication. Pharmacokinetic studies (PK) would be performed to estimate this point [ Time Frame: At 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]
  • To evaluate the tolerance and safety of the combination of Lopinavir-rtv+Nevirapine . [ Time Frame: over 48 weeks of treatment ] [ Designated as safety issue: Yes ]
  • To evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire). [ Time Frame: At 12, 24, 36 and 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 67
Study Start Date: October 2003
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
Drug: Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
No Intervention: 2
Nevirapine (Viramune): 1 comp (200mg)/12h
Drug: Nevirapine (Viramune): 1 comp (200mg)/12h
Nevirapine (Viramune): 1 comp (200mg)/12h

Detailed Description:

At the moment it is known that mitochondrial toxicity is the main pathogenic mechanism of toxicity associated with nucleoside analogues, including lipoatrophy, which at facial level is a stigmatising factor for patients with HIV infection.

The primary outcome measure of the design of an "NTRI-sparing" bitherapy is to retard the onset of mitochondrial toxicity or reverse it, mainly with regard to the loss of subcutaneous fat or lipoatrophy.

Lopinavir/ritonavir and nevirapine are two antiretrovirals with different mutation patterns and with high antiviral potency. Their combination therefore guarantees antiviral success. The NEKA study endorses efficacy immunologically and virologically (Negredo E. et al, NRTI-sparing regimen. XIV International AIDS Conference. Barcelona 2002. LB PeB9021).

Similarly, the protective effect of nevirapine on lipid metabolism would counteract the negative impact attributed to lopinavir/ritonavir, reducing cardiovascular risk in these patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >= 18 years.
  2. HIV-1 infected patients.
  3. Patients on HAART therapy with PIs or NNRTIs.
  4. Patients with an undetectable viral load (<50/80 copies/mL) over the last 6 months (at least 2 determinations separated by 2 months).
  5. Hepatic tests < 5 times the normal value.
  6. Subject able to follow the treatment period.
  7. Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
  8. Signature of the informed consent

Exclusion Criteria:

  1. Presence of opportunistic infections and/or recent tumours (< 6 months).
  2. Suspicion of resistance or documented resistance to any of the investigational drugs.
  3. Suspicion of possible bad adherence.
  4. Pregnancy or breastfeeding; refusal to follow reliable contraception over the treatment period.
  5. Known allergic hypersensitivity to any of the investigational drugs or any similar drug.
  6. Patients participating in another clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335686

Locations
Spain
Hospital C. Universitario de Santiago
Santiago, A Coruña, Spain, 15706
Hospital General Universitario de Elche
Elche, Alicante, Spain, 03203
Hospital Can Mises
Ibiza, Baleares, Spain, 07800
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de Granollers
Granollers, Barcelona, Spain, 08400
Mutua de Terrassa
Terrassa, Barcelona, Spain, 08221
Hospital General de Castellón
Castello, Castellón, Spain, 12004
Hospital de Figueres
Figueres, Girona, Spain, 17600
Hospital de Palamós
Palamós, Girona, Spain, 17230
Hospital Virgen del Toro
Mahón, Menorca, Spain, 07701
Hospital Nuestra Señora del Rosell
Cartagena, Murcia, Spain, 30071
Hospital C. Universitario Virgen de la Victoria
Malaga, Málaga, Spain, 29010
Hospital Costa del Sol
Marbella, Málaga, Spain, 29600
Hospital Central de Asturias
Asturias, Oviedo, Spain, 33006
Hospital Sant Joan de Reus
Reus, Tarragona, Spain, 43201
Hospital General Universitario de Alicante
Alicante, Spain, 03010
Hospital de Mataró
Barcelona, Spain, 08304
Hospital de Sant Pau
Barcelona, Spain, 08025
Hospital C. San Carlos
Madrid, Spain, 28040
Hospital Marqués de Valdecilla
Santander, Spain, 39008
Hospital Universitario Joan XXIII de Tarragona
Tarragona, Spain, 43007
Hospital Clínico de Valencia
Valencia, Spain, 46010
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Hospital Xeral Cies de Vigo
Vigo, Spain, 36204
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Investigators
Principal Investigator: Bonaventura Clotet, MD,PhD Lluita contra la Sida Foundation-HIV Unit
  More Information

No publications provided by Germans Trias i Pujol Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: LLuita Sida Foundation
ClinicalTrials.gov Identifier: NCT00335686     History of Changes
Other Study ID Numbers: MULTINEKA
Study First Received: June 8, 2006
Last Updated: February 19, 2008
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Mitochondrial toxicity
Lopinavir-rtv
Nevirapine
DNA mitochondrial/DNA nuclear

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Nevirapine
Lopinavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on August 25, 2014