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Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) With Darunavir/Ritonavir (DRV/r) (PEPDar)

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ClinicalTrials.gov Identifier: NCT01516970
Recruitment Status : Completed
First Posted : January 25, 2012
Results First Posted : October 11, 2016
Last Update Posted : July 19, 2017
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag G.m.b.H

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Human Immunodeficiency Virus (HIV)
Interventions Drug: Darunavir/Ritonavir (DRV/r)
Drug: Lopinavir in fixed combination with Ritonavir
Drug: Zidovudine
Drug: NRTIs
Drug: Efavirenz
Enrollment 312
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator. Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
Period Title: Overall Study
Started 159 153
Completed 141 132
Not Completed 18 21
Reason Not Completed
Lost to Follow-up             7             8
Adverse Event             1             5
Withdrawal by Subject             1             1
Other             9             7
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP) Total
Hide Arm/Group Description Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator. Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator. Total of all reporting groups
Overall Number of Baseline Participants 159 153 312
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 159 participants 153 participants 312 participants
34.2  (9.2) 32.3  (9.3) 33.3  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 159 participants 153 participants 312 participants
Female
28
  17.6%
28
  18.3%
56
  17.9%
Male
131
  82.4%
125
  81.7%
256
  82.1%
1.Primary Outcome
Title Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP)
Hide Description Number of participants with early discontinuation from randomized HIV PEP for any reason other than confirmation of the negative HIV infection status of the index person in participants receiving HIV PEP for at least 28 days and a maximum of 30 days was assessed. Per protocol (PP) population included all participants in modified intention-to-treat (mITT [defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person]) excluding participants with: No indication for HIV PEP; Initiation of PEP >72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.
Time Frame Up to 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PP population.
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description:
Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Overall Number of Participants Analyzed 155 150
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
10
(3.5 to 11.5)
15
(6.2 to 15.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP), Standard of Care Postexposure Prophylaxis (SOCPEP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2434
Comments The discontinuation rates were compared with a statistical test (Cochran-Mantel-Haenszel [CMH]-Test) with p-value: 0.2434
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) is defined to be non-treatment-emergent if the onset date of the AE was clearly before the date of first HIV PEP administration, otherwise it is considered treatment-emergent.
Time Frame Up to Month 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description:
Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Overall Number of Participants Analyzed 159 153
Measure Type: Number
Unit of Measure: participants
131 125
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP), Standard of Care Postexposure Prophylaxis (SOCPEP)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8839
Comments The percentage of participants with TEAEs were compared with a statistical test (Fisher's Exact Test) with p-value: 0.8839.
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Worst Sheehan Disability Scale (SDS) Score for the Safety Population
Hide Description The Sheehan Disability Scale (SDS) assesses functional impairment in 3 inter-related domains: work/school, social and family life, using a rating scale for each item ranging from 0 (not at all) to 10 (extremely).
Time Frame Month 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least 1 dose of randomized HIV PEP.
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description:
Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Overall Number of Participants Analyzed 159 153
Mean (Standard Deviation)
Unit of Measure: units on a scale
Impairment in work/school/studies 2.566  (2.775) 3.503  (2.940)
Impairment in social life 2.465  (2.594) 3.464  (2.786)
Impairment in family life 2.226  (2.624) 2.954  (2.713)
4.Secondary Outcome
Title Percentage of Participants Who Developed Detectable HIV Antibodies
Hide Description Seroconversion rate of HIV antibodies while receiving HIV PEP evaluated as the percentage of participants who developed detectable HIV antibodies (defined as positive) and percentage of participants who had not developed detectable HIV antibodies (defined as negative). Per protocol (PP) population included all participants in mITT (defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person) excluding participants with: No indication for HIV PEP; Initiation of PEP >72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.
Time Frame At Month 3
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on PP population. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description:
Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Overall Number of Participants Analyzed 138 133
Measure Type: Number
Unit of Measure: percentage of participants
Negative 99.3 100
Positive 0.7 0
Time Frame Up to Month 3
Adverse Event Reporting Description The safety population included all participants who received at least 1 dose of randomized HIV PEP.
 
Arm/Group Title Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Hide Arm/Group Description Darunavir (800 milligram [mg]) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs). The NRTIs (including tenofovir/emtricitabine [Truvada] was administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator. Standard of care human immunodeficiency virus (HIV) PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner. Lopinavir in combination with low-dose ritonavir (LPV/r) [Kaletra] was combined with following NRTIs: TDF (tenofovir)/ FTC (emtricitabine) [Truvada], AZT (zidovudine)/3TC (lamivudine) [Combivir]) and ABC (Abacavir)/ 3TC (Lamivudine) administered as per the individual SmPCs at the discretion of either the treating physician or Investigator.
All-Cause Mortality
Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Affected / at Risk (%) Affected / at Risk (%)
Total   1/159 (0.63%)   0/153 (0.00%) 
Psychiatric disorders     
Depression * 1 [1]  1/159 (0.63%)  0/153 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 16.0
[1]
The only serious adverse event observed in the DRV/r arm was a hospitalization due to an unrelated depression.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Darunavir/Ritonavir Postexposure Prophylaxis (DRV/r PEP) Standard of Care Postexposure Prophylaxis (SOCPEP)
Affected / at Risk (%) Affected / at Risk (%)
Total   96/159 (60.38%)   111/153 (72.55%) 
Gastrointestinal disorders     
Abdominal Pain Upper * 1  14/159 (8.81%)  11/153 (7.19%) 
Diarrhoea * 1  45/159 (28.30%)  76/153 (49.67%) 
Flatulence * 1  5/159 (3.14%)  11/153 (7.19%) 
Nausea * 1  24/159 (15.09%)  41/153 (26.80%) 
Vomiting * 1  10/159 (6.29%)  9/153 (5.88%) 
General disorders     
Asthenia * 1  5/159 (3.14%)  1/153 (0.65%) 
Fatigue * 1  21/159 (13.21%)  28/153 (18.30%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  5/159 (3.14%)  4/153 (2.61%) 
Nervous system disorders     
Dizziness * 1  6/159 (3.77%)  2/153 (1.31%) 
Dysgeusia * 1  1/159 (0.63%)  5/153 (3.27%) 
Headache * 1  19/159 (11.95%)  8/153 (5.23%) 
Psychiatric disorders     
Sleep Disorder * 1  0/159 (0.00%)  6/153 (3.92%) 
Skin and subcutaneous tissue disorders     
Rash * 1  7/159 (4.40%)  4/153 (2.61%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Name/Title: Medical Leader, Medical Department
Organization: Janssen-Cilag GmbH
Responsible Party: Janssen-Cilag G.m.b.H
ClinicalTrials.gov Identifier: NCT01516970     History of Changes
Other Study ID Numbers: CR018349
TMC114IFD3004 ( Other Identifier: Janssen-Cilag G.m.b.H, Germany )
2011-001303-13 ( EudraCT Number )
First Submitted: October 11, 2011
First Posted: January 25, 2012
Results First Submitted: June 20, 2016
Results First Posted: October 11, 2016
Last Update Posted: July 19, 2017