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Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00078403
First Posted: February 25, 2004
Last Update Posted: January 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
Results First Submitted: November 5, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: HIV Infections
Hepatitis C
Liver Disease
Interventions: Drug: Peginterferon alfa-2a
Drug: Ribavirin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
People with hepatitis C virus (HCV)/HIV coinfection were recruited for participation in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
330 participants were to receive 12 weeks of PEG+RBV to determine EVR status. Of the 330, 33 discontinued prior to week 12; 113 were non-EVRs, 80 of whom were randomized between Arms A and B; and 184 achieved EVR, 170 of whom were eligible to continue. 169 of the 170 were assigned to Arm C and one was inadvertently randomized between Arms A and B.

Reporting Groups
  Description
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Participant Flow:   Overall Study
    Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)   OL (PEG-IFN, RBV) Then OL Randomized (Observation)   OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
STARTED   44 [1]   42 [2]   169 
COMPLETED   26   26   141 
NOT COMPLETED   18   16   28 
[1] Eligible at pre-assignment (40), direct (2), Arm C week 36 non-response (1), EVR inadvertently (1).
[2] Eligible at pre-assignment (40), direct (1), Arm C week 36 non-response (1).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Arm A, B and C participants.

Reporting Groups
  Description
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA >=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA <600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly & RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA >=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.
Total Total of all reporting groups

Baseline Measures
   Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)   OL (PEG-IFN, RBV) Then OL Randomized (Observation)   OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)   Total 
Overall Participants Analyzed 
[Units: Participants]
 44   42   169   255 
Age 
[Units: Participants]
Count of Participants
       
<=18 years      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      44 100.0%      42 100.0%      169 100.0%      255 100.0% 
>=65 years      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Age 
[Units: Years]
Mean (Standard Deviation)
 48.8  (6.7)   48.1  (5.8)   47.2  (7.1)   47.6  (6.8) 
Gender 
[Units: Participants]
Count of Participants
       
Female      12  27.3%      12  28.6%      19  11.2%      43  16.9% 
Male      32  72.7%      30  71.4%      150  88.8%      212  83.1% 
Region of Enrollment 
[Units: Participants]
       
United States   41   40   168   249 
Puerto Rico   3   2   1   6 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)   [ Time Frame: Baseline and at week 72 or premature discontinuation ]

2.  Secondary:   Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)   [ Time Frame: Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84 ]

3.  Secondary:   Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)   [ Time Frame: Baseline and at week 72 or premature discontinuation ]

4.  Secondary:   Number of Participants With Anemia   [ Time Frame: Up to 96 weeks ]

5.  Secondary:   Number of Participants With Neutropenia   [ Time Frame: Up to 96 weeks ]

6.  Secondary:   Number of Participants With Thrombocytopenia   [ Time Frame: Up to 96 weeks ]

7.  Secondary:   Number of Participants With Depression and/or Other Psychological Events   [ Time Frame: Up to 96 weeks ]

8.  Secondary:   Number of Participants With High-grade Signs and Symptoms or Laboratory Values   [ Time Frame: Up to 96 Weeks ]

9.  Secondary:   Number of Participants With Dose Modifications, Temporary Stops, and Premature Treatment Discontinuations   [ Time Frame: Up to 96 Weeks ]

10.  Secondary:   Number of Participants Adherent to Study Medications   [ Time Frame: Arm A: at weeks 12, 24, 48 and 72. Arm C: at entry and weeks 12, 24, 48, 60. ]

11.  Secondary:   HCV Polymorphisms   [ Time Frame: Entry and week 72 (Arms A and B only). ]

12.  Secondary:   HCV-specific Immune Response in Intrahepatic Lymphocytes   [ Time Frame: Entry and week 72 (Arms A and B only). ]

13.  Secondary:   Number of Participants With Undetectable HIV Viral Load (<50 Copies/mL)   [ Time Frame: Arms A and B: Weeks 0, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 48, 60, 72, 84 ]

14.  Secondary:   Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)   [ Time Frame: Arms A and B: at entry and weeks 24, 48 and 72; Arm C: at entry and at weeks 12, 24, 36, 48, 72, 84 and 96. ]

15.  Secondary:   Sustained Virologic Response   [ Time Frame: 24 weeks after end of treatment ]

16.  Secondary:   Number of Participants Who Used Antianorexia Agents, Such as Megestrol and Dronabinol   [ Time Frame: Up to 96 weeks ]

17.  Secondary:   Number of Participants With Prescription as Needed of Erythropoietin (EPO), Granulocyte Colony-stimulating Factor (GCSF), and Granulocyte-monocyte Colony-stimulating Factor (GM-CSF)   [ Time Frame: At any time after pre-assignment ]

18.  Secondary:   Weight   [ Time Frame: Arms A and B: at entry and weeks 4, 8, 12, 16, 24, 32, 40, 48, 56, 64 and 72; Arm C: at entry and weeks 4, 8, 12, 16, 24, 36, 48, 72, 84 and 96. ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame From entry (Step 2 for Arms A and B, Step 3 for Arm C) to study completion (at Week 72 for Step 2; at week 78-84 for Step 3, depending on participants' time in Step 1).
Additional Description The protocol required reporting of signs/symptoms and laboratory results >=Grade 3 and events that led to a change in treatment, regardless of grade. Hemoglobin, plateles, ANC, fasting HDL, LDL and total cholesterol, insulin and glucose values were reported regardless of grade. The DAIDS AE Grading Table (1992) and Expedited AE Manual (2004) were used.

Reporting Groups
  Description
Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN) At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to receive the pegylated interferon (PEG-IFN) 180 mcg weekly Arm.
OL (PEG-IFN, RBV) Then OL Randomized (Observation) At week 12 (end of the initial run-in period – Step 1) participants were found to be HCV RNA positive (HCV RNA > 60 IU/mL) and had less than a 2 log decrease in HCV RNA from Baseline. For Step 2, participants were assigned to the Randomized Open Label (OL) part of the study to be followed on the Observation (no treatment) Arm.
OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV) At week 12 (end of initial run-in period, Step 1) participants were found to be HCV RNA negative (HCV RNA < 60 IU/mL) or had more than a 2 log decrease in HCV RNA from Baseline. Participants were assigned to remain in the Open Label (OL) part of the study continuing the run-in treatment (PEG-IFN 180 mcg weekly & ribavirin [RBV] 1-1.2 g/day based on weight). At the beginning of week 36, participants were retested and, if found to be HCV RNA positive (HCV RNA > 60 IU/mL), participants could be randomized to OL PEG-IFN or Observation.

Serious Adverse Events
    Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)   OL (PEG-IFN, RBV) Then OL Randomized (Observation)   OL (PEG-IFN, RBV) Then OL (PEG-IFN, RBV)
Total, Serious Adverse Events       
# participants affected / at risk   6/44 (13.64%)   2/42 (4.76%)   37/169 (21.89%) 
Blood and lymphatic system disorders       
Anaemia † 1       
# participants affected / at risk   1/44 (2.27%)   0/42 (0.00%)   2/169 (1.18%) 
Bone marrow failure † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Neutropenia † 1       
# participants affected / at risk   2/44 (4.55%)   0/42 (0.00%)   13/169 (7.69%) 
Thrombocytopenia † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Cardiac disorders       
Cardiac arrest † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Coronary artery disease † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Myocardial infarction † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Endocrine disorders       
Basedow's disease † 1       
# participants affected / at risk   0/44 (0.00%)   1/42 (2.38%)   0/169 (0.00%) 
Hypothyroidism † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Gastrointestinal disorders       
Abdominal pain † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Pancreatitis † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   2/169 (1.18%) 
General disorders       
Death † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Pyrexia † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Infections and infestations       
Pneumonia † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Injury, poisoning and procedural complications       
Overdose † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Investigations       
Blood triglycerides increased † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Electrocardiogram QT prolonged † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Haemoglobin decreased † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Neutrophil count † 1       
# participants affected / at risk   1/44 (2.27%)   1/42 (2.38%)   0/169 (0.00%) 
Neutrophil count decreased † 1       
# participants affected / at risk   1/44 (2.27%)   1/42 (2.38%)   3/169 (1.78%) 
Metabolism and nutrition disorders       
Hyperglycaemia † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Hypertriglyceridaemia † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cerebellar tumour † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Lung neoplasm malignant † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Lymphoma † 1       
# participants affected / at risk   1/44 (2.27%)   0/42 (0.00%)   0/169 (0.00%) 
Neoplasm † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Prostate cancer † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Squamous cell carcinoma † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Psychiatric disorders       
Abnormal dreams † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea † 1       
# participants affected / at risk   1/44 (2.27%)   0/42 (0.00%)   0/169 (0.00%) 
Pulmonary embolism † 1       
# participants affected / at risk   0/44 (0.00%)   0/42 (0.00%)   1/169 (0.59%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (13.0)




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com


Publications of Results:
Other Publications:
The Division of AIDS Table for Grading the Severity of Adult Adverse Events (DAIDS AE Grading Table), August 1992.
Manual for Expedited Reporting of Adverse Events to Division of AIDS (DAIDS EAE Manual), May 2004.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00078403     History of Changes
Other Study ID Numbers: A5178
10008 ( Registry Identifier: DAIDS ES Registry Number )
First Submitted: February 24, 2004
First Posted: February 25, 2004
Results First Submitted: November 5, 2010
Results First Posted: April 27, 2011
Last Update Posted: January 27, 2017