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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335686
• Other study ID #: MULTINEKA
• Status: Completed
• Phase: Phase 4
• First received: June 8, 2006
• Last updated: February 19, 2008
• Start date: October 2003
• Est. completion date: March 2006

Study information

• Verified date: June 2007
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: March 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
• Nevirapine (Viramune): 1 comp (200mg)/12h
Nevirapine (Viramune): 1 comp (200mg)/12h

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Central de Asturias	Asturias	Oviedo
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de Mataró	Barcelona
Spain	Hospital de Sant Pau	Barcelona
Spain	Hospital Nuestra Señora del Rosell	Cartagena	Murcia
Spain	Hospital General de Castellón	Castello	Castellón
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital de Figueres	Figueres	Girona
Spain	Hospital de Granollers	Granollers	Barcelona
Spain	Hospital Can Mises	Ibiza	Baleares
Spain	Hospital C. San Carlos	Madrid
Spain	Hospital Virgen del Toro	Mahón	Menorca
Spain	Hospital C. Universitario Virgen de la Victoria	Malaga	Málaga
Spain	Hospital Costa del Sol	Marbella	Málaga
Spain	Hospital de Palamós	Palamós	Girona
Spain	Hospital Sant Joan de Reus	Reus	Tarragona
Spain	Hospital Marqués de Valdecilla	Santander
Spain	Hospital C. Universitario de Santiago	Santiago	A Coruña
Spain	Hospital Universitario Joan XXIII de Tarragona	Tarragona
Spain	Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital Xeral Cies de Vigo	Vigo

Sponsors (2)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital	Fundacio Lluita Contra la SIDA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit.		At 24 and 48 weeks with regard to the baseline visit	No
Secondary	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		At 12, 24, 36 and 48 weeks.	No
Secondary	and CV<50 copies/mL over at last 6 months		At 12, 24, 36 and 48 weeks	No
Secondary	To determine whether the combination with Lopinavir/rtv +Nevirapine is efficacious in avoiding progression to lipoatrophy/lipodystrophy or else the reversal thereof		At 24 and 48 weeks	No
Secondary	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		At 12, 24, 36 and 48 weeks.	No
Secondary	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		At 12, 24, 36 and 48 weeks	No
Secondary	To evaluate the tolerance and safety of the combination of Lopinavir-rtv+Nevirapine .		over 48 weeks of treatment	Yes
Secondary	To evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire).		At 12, 24, 36 and 48 weeks	No