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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.

Sponsors and Collaborators: Germans Trias i Pujol Hospital
FUNDACIÓ LLUITA CONTRA LA SIDA
Information provided by: Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier: NCT00335686
  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 IV

MedlinePlus related topics:   AIDS   

ChemIDplus related topics:   Nevirapine    Lopinavir   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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

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
1: No Intervention
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
2: No Intervention
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

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

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

Sponsors and Collaborators
Germans Trias i Pujol Hospital
FUNDACIÓ LLUITA CONTRA LA SIDA

Investigators
Principal Investigator:     Bonaventura Clotet, MD,PhD     Lluita contra la Sida Foundation-HIV Unit    
  More Information


Responsible Party:   LLuita Sida Foundation ( LLuita Sida Foundation )
Study ID Numbers:   MULTINEKA
First Received:   June 8, 2006
Last Updated:   February 19, 2008
ClinicalTrials.gov Identifier:   NCT00335686
Health Authority:   Spain: Ministry of Health

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

Study placed in the following topic categories:
Virus Diseases
Nevirapine
Sexually Transmitted Diseases, Viral
Lopinavir
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Slow Virus Diseases
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 14, 2008




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