A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)

Acquired Immunodeficiency Syndrome Clinical Trial

Official title:

An Open-label Study Evaluating the Resistance Profile of Single Dose Nevirapine(NVP) When Combined With a 4 or 7 Day Course of Combivir® (ZDV/3TC) Compared to Single Dose Nevirapine for the Prevention of Mother to Child Transmission (pMTCT) of HIV - Treatment Options Preservation Study (T.O.P.S.)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00144183
• Other study ID #: 1100.1413
• Secondary ID: MCC;N2/19/8/2(19
• Status: Completed
• Phase: Phase 3
• First received: September 2, 2005
• Last updated: November 1, 2013
• Start date: January 2003
• Est. completion date: January 2007

Study information

• Verified date: November 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial Summary

To determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir®, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.

Description:

An open-label, randomised, multicentre study to determine whether a regimen of single dose nevirapine combined with either 4 or 7 days of Combivir, compared to a regimen of single dose nevirapine, for the prevention of mother to child transmission can reduce the rate of development of drug resistant mutations of HIV-1, in HIV-1 infected pregnant women, who have not received antiretroviral therapy previously.

An interim analysis of the first 61 patients showed that a clinical and statistical difference exists between the occurrence of HIV-1 NNRTI resistant mutations in the single dose nevirapine only arm (50%) and the two other combination arms (9%). These findings partially answered the objectives outlined in the initial objectives. Consequently enrolment onto the single dose nevirapine arm was terminated. The objective of the trial was modified to compare whether either the 4 or the 7 day combination of ZDV+3TC and nevirapine would result in any significant reduction in the incidence of nevirapine resistance.

Study Hypothesis:

Evaluations of HIV-1 resistance patterns in trials of pMTCT have demonstrated nevirapine resistant HIV-1 isolates in approximately 15-20% of mothers 4-6 weeks after receiving either a single or two dose 200mg nevirapine regimen. Although the ability to detect these genotypic mutations decreases to 0% by about 18 months, it is not clear whether this resistance is clinically significant.(HIVNET 012).

Empirically then it would seem useful to develop a strategy to diminish the emergence of this early resistance, therefore this study is proposed to evaluate whether the effect of 4 or 7 days of 3TC+ ZDV added to a single dose nevirapine regimen for the prevention of MTCT will prevent the emergence of resistance to nevirapine.

Comparison(s):

ACTG 076, Thai, PETRA , HIVNET 006/012, SAINT

Recruitment information / eligibility

• Status: Completed
• Enrollment: 407
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnant women identified at antenatal clinics after from 34 weeks gestation and who are antiretroviral drug naive.

• Mothers with a documented positive HIV Rapid test confirmed by a detectable HI V-1 RNA PCR (viral load).

• Mother to have a screening viral load of > 2000 RNA copies/mL.

Exclusion Criteria:

• Mothers who, in the opinion of the investigator ,cannot be relied on to return with their infants for postnatal visits.

• Mothers who have received any antiretroviral drugs previously.

• Clinical suspicion of intra-uterine foetal death

• Unwillingness or inability to reasonably comply with the protocol requirements.

• Use of any other investigational product during the pregnancy and for the dura tion of the study period.

• Patients with a recent history of pancreatitis or peripheral neuropathy.

• Patients with renal failure requiring dialysis.

• Patients with evidence of hepatic dysfunction as measured by total bilirubin > 2.5 times ULN or AST/ALT > 5 times ULN at the screening visit.

• Patients with any one of the following additional laboratory abnormalities at screening : Haemoglobin concentration < 7.5 g/dl. Neutrophil count < 750 cells/mm3. Platelet count < 75,000 cells/mm3. Serum amylase > 2 x ULN.

• recent history ( during the pregnancy) of drug abuse or alcoholism.

• Mothers who will undergo elective caesarean section.

• If known prior to delivery, mothers with foetuses with anomalies incompatible with life.

Study Design

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Nevirapine (NVP)
Nevirapine 200mg once daily for 14 days followed by 200mg twice daily thereafter for the remainder of the treatment period. Combivir®, one tablet twice daily.
• Zidovudine (ZCV)

• 3TC

Locations

Country	Name	City	State
South Africa	Boehringer Ingelheim Investigational Site	Attridgeville
South Africa	Boehringer Ingelheim Investigational Site	Cape Town
South Africa	Boehringer Ingelheim Investigational Site	Durban
South Africa	Boehringer Ingelheim Investigational Site	Johannesburg
South Africa	Boehringer Ingelheim Investigational Site	Soweto

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of mothers with HIV-1 isolates with new NNRTI (Non Nucleoside Reverse Transcriptase Inhibitor) resistance-associated mutations identified by genotype testing		6 weeks following delivery	No

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