Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Interleukin-2 Plus Antiretroviral Therapy for HIV-Infected Patients With Low CD4+ Counts (SILCAAT Study) (SILCAAT)

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00013611
First received: March 24, 2001
Last updated: August 2, 2011
Last verified: August 2011
Results First Received: November 8, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infection
Intervention: Drug: Proleukin

  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
1971 participants were randomized at 139 sites in 11 countries. The first randomization was on 30 April 1999 and the last randomization was on 28 September 2002. Sites who re-consented 2/3 or more of their participants to Version 3 of the protocol were included in the analysis cohort. There are 1695 participants in the analysis cohort.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Proleukin Plus Antiretroviral Therapy Patients receive an initial dose of 4.5 MIU of proleukin twice daily for 5 consecutive days every 8 weeks during the first year (6 cycles total). After the first year, additional cycles are given to either achieve or maintain the patient's CD4+ count goal. CD4+ goal is defined as an increase of 125 cells/cubic mm for participants in the 50-199 CD4+ count stratum, and an increase of 175 cells/cubic mm for participants in the 200-299 CD4+ stratum. In addition, all patients must be prescribed combination antiretroviral drug treatment. The choice of combination therapy is left to the discretion of the treating clinician. Investigators will use their national guidelines for determining when antiretroviral therapy should be changed and for when determining when therapy should be used. All patients must take antiretroviral therapy during each 5-consecutive-day treatment cycle.
Antiretroviral Therapy Only All patients must be prescribed combination antiretroviral drug treatment. The choice of combination therapy is left to the discretion of the treating clinician. Investigators will use their national guidelines for determining when antiretroviral therapy should be changed and for when determining when therapy should be used.

Participant Flow:   Overall Study
    Proleukin Plus Antiretroviral Therapy   Antiretroviral Therapy Only
STARTED   849 [1]   846 [1] 
COMPLETED   758   746 
NOT COMPLETED   91   100 
Lost to Follow-up                91                100 
[1] 138 were excluded from sites that did not re-consent 2/3 of patients to the amended protocol in 2003



  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.
No text entered.

Reporting Groups
  Description
Proleukin Plus Antiretroviral Therapy No text entered.
Antiretroviral Therapy Only No text entered.
Total Total of all reporting groups

Baseline Measures
   Proleukin Plus Antiretroviral Therapy   Antiretroviral Therapy Only   Total 
Overall Participants Analyzed 
[Units: Participants]
 849   846   1695 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   841   838   1679 
>=65 years   8   8   16 
Age 
[Units: Years]
Mean (Standard Deviation)
 41.8  (8.7)   42.0  (8.8)   41.9  (8.7) 
Gender 
[Units: Participants]
     
Female   137   143   280 
Male   712   703   1415 
Region of Enrollment 
[Units: Participants]
     
Belgium   16   13   29 
Germany   50   46   96 
Spain   139   131   270 
France   47   50   97 
Italy   131   142   273 
Netherlands   11   12   23 
Argentina   85   85   170 
Australia   62   64   126 
United States   203   203   406 
Canada   68   62   130 
Brazil   37   38   75 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   New or Recurrent Disease Progression Events, as Defined, or Death.   [ Time Frame: From randomization to date last known to be alive or November 15, 2008, whichever is earlier ]

2.  Secondary:   All-cause Mortality   [ Time Frame: From randomization to date last known to be alive or November 15, 2008, whichever is earlier ]

3.  Secondary:   New or Recurrent Disease Progression Events   [ Time Frame: From randomization to date last known to be alive or November 15, 2008, whichever is earlier ]

4.  Secondary:   Grade 4 Clinical Events   [ Time Frame: From randomization to date last known to be alive or November 15, 2008, whichever is earlier ]

5.  Secondary:   CD4+ Cell Count   [ Time Frame: Every 4 months from randomization through date last known to be alive or November 15, 2008, whichever was earliest . ]

6.  Secondary:   New or Recurrent Serious Disease Progression Events or Death   [ Time Frame: From randomization to date last known to be alive or November 15, 2008, whichever is earlier ]


  Serious Adverse Events
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Time Frame From randomization to date last known to be alive or November 15, 2008, whichever is earlier
Additional Description

Adverse events are defined as Grade 4 events not due to progression of HIV disease.

Serious and/or other [non-serious) adverse events were not collected/assessed. Other Adverse Events were not collected.


Reporting Groups
  Description
Proleukin Plus Antiretroviral Therapy No text entered.
Antiretroviral Therapy Only No text entered.

Serious Adverse Events
    Proleukin Plus Antiretroviral Therapy   Antiretroviral Therapy Only
Total, serious adverse events     
# participants affected / at risk   203/849 (23.91%)   186/846 (21.99%) 
Blood and lymphatic system disorders     
Aneamias nonhaemolytic and marrow depression     
# participants affected / at risk   3/849 (0.35%)   6/846 (0.71%) 
# events   5   6 
Haemolyses and related conditions     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Platelet disorders     
# participants affected / at risk   2/849 (0.24%)   0/846 (0.00%) 
# events   2   0 
Spleen, lymphatic and reticuloendothelial system disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
White blood cell disorders     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Cardiac disorders     
Cardiac arrythmias     
# participants affected / at risk   4/849 (0.47%)   4/846 (0.47%) 
# events   5   5 
Cardiac disorder signs and symptoms     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Cornoary artery disorders     
# participants affected / at risk   20/849 (2.36%)   20/846 (2.36%) 
# events   29   24 
Heart failures     
# participants affected / at risk   3/849 (0.35%)   6/846 (0.71%) 
# events   3   13 
Myocardial disorders     
# participants affected / at risk   1/849 (0.12%)   2/846 (0.24%) 
# events   1   2 
Pericardial disorders     
# participants affected / at risk   2/849 (0.24%)   1/846 (0.12%) 
# events   2   1 
Cardiac valve disorders     
# participants affected / at risk   2/849 (0.24%)   1/846 (0.12%) 
# events   2   2 
Congenital, familial and genetic disorders     
Renal and urinary tract disoerders congenital     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Endocrine disorders     
Endocrine disorders of gonadal function     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Thyroid gland disorders     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   3 
Eye disorders     
Ocular neuromuscular disorders     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Gastrointestinal disorders     
Abdominal hernias and other adominal wall conditions     
# participants affected / at risk   5/849 (0.59%)   0/846 (0.00%) 
# events   5   0 
Diverticular disorders     
# participants affected / at risk   1/849 (0.12%)   2/846 (0.24%) 
# events   1   2 
Exocrine pancreas conditions     
# participants affected / at risk   6/849 (0.71%)   6/846 (0.71%) 
# events   13   7 
Gastrointestinal condictions NEC     
# participants affected / at risk   2/849 (0.24%)   1/846 (0.12%) 
# events   2   1 
Gastrointestinal haemorrhages NEC     
# participants affected / at risk   13/849 (1.53%)   5/846 (0.59%) 
# events   15   10 
Gastrointestinal inflammatory conditions     
# participants affected / at risk   4/849 (0.47%)   3/846 (0.35%) 
# events   4   5 
Gastrointestinal motility and defaecation conditions     
# participants affected / at risk   6/849 (0.71%)   5/846 (0.59%) 
# events   8   9 
Gastrointestinal stenosis and obstructions     
# participants affected / at risk   5/849 (0.59%)   3/846 (0.35%) 
# events   9   3 
Gastrointestinal signs and symptoms     
# participants affected / at risk   4/849 (0.47%)   2/846 (0.24%) 
# events   4   2 
Gastrointestinal ulceration and perforation     
# participants affected / at risk   5/849 (0.59%)   3/846 (0.35%) 
# events   5   3 
Gastrointestinal vascular conditions     
# participants affected / at risk   7/849 (0.82%)   2/846 (0.24%) 
# events   9   3 
Peritoneal and retrooperationael conditions     
# participants affected / at risk   2/849 (0.24%)   4/846 (0.47%) 
# events   2   4 
General disorders     
Body temperature conditions     
# participants affected / at risk   3/849 (0.35%)   2/846 (0.24%) 
# events   4   2 
General system disorders NEC     
# participants affected / at risk   6/849 (0.71%)   3/846 (0.35%) 
# events   6   4 
Fatal outcomes     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Therapeutic and nontherapeutic effects (excl toxicity)     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Hepatobiliary disorders     
Bile duct disorders     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   3 
Gallbladder disorders     
# participants affected / at risk   4/849 (0.47%)   7/846 (0.83%) 
# events   4   7 
Hepatic and hepatobiliary disorders     
# participants affected / at risk   20/849 (2.36%)   10/846 (1.18%) 
# events   26   14 
Immune system disorders     
Allergic conditions     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Immune disorders NEC     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Infections and infestations     
Bacterial infectious disorders     
# participants affected / at risk   14/849 (1.65%)   18/846 (2.13%) 
# events   19   20 
Fungal infectious disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Infections - pathogen unspecified     
# participants affected / at risk   28/849 (3.30%)   27/846 (3.19%) 
# events   31   30 
Mycobacterial infectious disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Viral infectious disorders     
# participants affected / at risk   11/849 (1.30%)   11/846 (1.30%) 
# events   11   16 
Injury, poisoning and procedural complications     
Bone and joint injuries     
# participants affected / at risk   6/849 (0.71%)   3/846 (0.35%) 
# events   6   3 
Injuries NEC     
# participants affected / at risk   2/849 (0.24%)   5/846 (0.59%) 
# events   3   5 
Procedural and device related injuries and complications NEC     
# participants affected / at risk   1/849 (0.12%)   5/846 (0.59%) 
# events   1   5 
Medications errors     
# participants affected / at risk   2/849 (0.24%)   3/846 (0.35%) 
# events   2   3 
Chemical injury and poisoning     
# participants affected / at risk   1/849 (0.12%)   2/846 (0.24%) 
# events   1   2 
Investigations     
Gastrointestinal investigations     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Hepatobiliary investigations     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Lipid analyses     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Metabolic, nutritional and blood gas investigations     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Metabolism and nutrition disorders     
Acid-base disorders     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Appetite and general nutritional disorders     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
Electrolyte and fluid balance conditions     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Glucose metabolism disorders (incl diabetes mellitus)     
# participants affected / at risk   4/849 (0.47%)   1/846 (0.12%) 
# events   9   1 
Purine and pyrimidine metabolism disorders     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Musculoskeletal and connective tissue disorders     
Bone disorders (excl congenital and fractuers)     
# participants affected / at risk   6/849 (0.71%)   2/846 (0.24%) 
# events   7   2 
Joint disorders     
# participants affected / at risk   2/849 (0.24%)   6/846 (0.71%) 
# events   2   8 
Musculoskeletal and connective tissue deformities (incl intervertebral disc disorders)     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   3 
Musculoskeletal and connective tissue disorders NEC     
# participants affected / at risk   1/849 (0.12%)   2/846 (0.24%) 
# events   1   2 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Endocrine neoplasms malignant and unspecified     
# participants affected / at risk   2/849 (0.24%)   1/846 (0.12%) 
# events   2   2 
Gastrointestinal neoplasms malignant and unspecified     
# participants affected / at risk   7/849 (0.82%)   10/846 (1.18%) 
# events   9   11 
Hepatic and biliary neoplasms benign     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Hepatobiliary neoplasms malignant and unspecified     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Leukaemias     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Mesotheliomas     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Metastases     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
Miscellaneuous and site unspecified neoplasms malignant and unspecified     
# participants affected / at risk   5/849 (0.59%)   3/846 (0.35%) 
# events   5   3 
Miscellaneous and site unspecified neoplasms benign     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Nervous system neoplasms malignant and unspecified NEC     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Renal and urinary tract neoplasms malignant and unspecified     
# participants affected / at risk   3/849 (0.35%)   1/846 (0.12%) 
# events   4   1 
Reproductive neoplasms female malignant and unspecified     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Reproductive neoplasms male malignant and unspecified     
# participants affected / at risk   5/849 (0.59%)   3/846 (0.35%) 
# events   5   3 
Respiratory and mediastinal neoplams malignant and unspecified     
# participants affected / at risk   12/849 (1.41%)   11/846 (1.30%) 
# events   14   13 
Skin neoplasms malignant and unspecified     
# participants affected / at risk   7/849 (0.82%)   4/846 (0.47%) 
# events   9   5 
Oncologic complications and emergencies     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Nervous system disorders     
Central nervous system vascular disorders     
# participants affected / at risk   9/849 (1.06%)   8/846 (0.95%) 
# events   9   10 
Cranial nerve disorders (excl neoplasms)     
# participants affected / at risk   1/849 (0.12%)   3/846 (0.35%) 
# events   1   3 
Encephalopathies     
# participants affected / at risk   2/849 (0.24%)   2/846 (0.24%) 
# events   2   2 
Headaches     
# participants affected / at risk   2/849 (0.24%)   0/846 (0.00%) 
# events   2   0 
Movement disorders (incl parkinsonism)     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Neurological disorders NEC     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
Neuromuscular disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Seizures (incl subtypes)     
# participants affected / at risk   3/849 (0.35%)   4/846 (0.47%) 
# events   4   4 
Spinal cord and nreve root disorders     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Structural brain disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Psychiatric disorders     
Anxiety disorders and symptoms     
# participants affected / at risk   3/849 (0.35%)   0/846 (0.00%) 
# events   3   0 
Cognitive and attention disorders and distrubances     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Deliria (incl confusion)     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Depressed mood disorders and disturbances     
# participants affected / at risk   7/849 (0.82%)   4/846 (0.47%) 
# events   8   4 
Manic and bipolar mood disorders and disturbances     
# participants affected / at risk   2/849 (0.24%)   0/846 (0.00%) 
# events   2   0 
Personality disorders and disturbances in behaviour     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   2 
Psychiatric disorders NEC     
# participants affected / at risk   4/849 (0.47%)   0/846 (0.00%) 
# events   5   0 
Schizophrenia and other psychotic disorders     
# participants affected / at risk   2/849 (0.24%)   0/846 (0.00%) 
# events   2   0 
Suicidal and self-injurious behaviours NEC     
# participants affected / at risk   10/849 (1.18%)   4/846 (0.47%) 
# events   11   4 
Renal and urinary disorders     
Nephropathies     
# participants affected / at risk   1/849 (0.12%)   4/846 (0.47%) 
# events   1   4 
Renal disorders (excl nephropathies)     
# participants affected / at risk   5/849 (0.59%)   12/846 (1.42%) 
# events   6   13 
Urinary tract signs and symptoms     
# participants affected / at risk   2/849 (0.24%)   2/846 (0.24%) 
# events   3   2 
Urolithiases     
# participants affected / at risk   4/849 (0.47%)   3/846 (0.35%) 
# events   6   3 
Reproductive system and breast disorders     
Breast disorders     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Cervix disorders (excl infections and inflammations)     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
Male reproductive tract infections and inflammations     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Prostatic disorders (excl infections and inflammations)     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Uterine, pelvic and broad ligament disorders     
# participants affected / at risk   0/849 (0.00%)   3/846 (0.35%) 
# events   0   3 
Vulvovaginal disorders (excl infections and inflammations)     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Respiratory, thoracic and mediastinal disorders     
Bronchial disorders (excl neoplasms)     
# participants affected / at risk   2/849 (0.24%)   4/846 (0.47%) 
# events   2   6 
Thoracic disorders (excl lung and pleura)     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Lower respiratory tract disorders (excl obstruction and infection)     
# participants affected / at risk   3/849 (0.35%)   3/846 (0.35%) 
# events   3   3 
Pleural disorders     
# participants affected / at risk   2/849 (0.24%)   1/846 (0.12%) 
# events   3   1 
Pulmonary vascular disorders     
# participants affected / at risk   3/849 (0.35%)   2/846 (0.24%) 
# events   3   2 
Respiratory disorders NEC     
# participants affected / at risk   4/849 (0.47%)   11/846 (1.30%) 
# events   4   12 
Upper respiratory tract disorders (excl infections)     
# participants affected / at risk   0/849 (0.00%)   1/846 (0.12%) 
# events   0   1 
Skin and subcutaneous tissue disorders     
Epidermal and dermal conditions     
# participants affected / at risk   3/849 (0.35%)   0/846 (0.00%) 
# events   3   0 
Skin and subcutaenous tissue disorders NEC     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
Surgical and medical procedures     
Vascular therapeutic procedures     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Nervous system, skull and spine therapeutic procedures     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Hepatobiliary therapeutic procedures     
# participants affected / at risk   1/849 (0.12%)   1/846 (0.12%) 
# events   1   1 
Vascular disorders     
Aneurysms and artery dissections     
# participants affected / at risk   2/849 (0.24%)   0/846 (0.00%) 
# events   3   0 
Arteriosclerosis, stenosis, vascular insufficiency and necrosis     
# participants affected / at risk   1/849 (0.12%)   2/846 (0.24%) 
# events   1   2 
Decreased and nonspecific blood pressure disorders and shock     
# participants affected / at risk   3/849 (0.35%)   3/846 (0.35%) 
# events   3   4 
Embolism and thrombosis     
# participants affected / at risk   4/849 (0.47%)   0/846 (0.00%) 
# events   4   0 
Vascular disorders NEC     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Vascular haemorrhagic disorders     
# participants affected / at risk   1/849 (0.12%)   0/846 (0.00%) 
# events   1   0 
Vascular hypertensive disorders     
# participants affected / at risk   0/849 (0.00%)   2/846 (0.24%) 
# events   0   2 
1 Term from vocabulary, MedDRA (12.0)




  Other Adverse Events


  Limitations and Caveats
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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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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Gary Collins, M.S.
Organization: University of Minnesota
phone: 612-626-9006
e-mail: gary-c@ccbr.umn.edu


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

Responsible Party: DAIDS, NIAID
ClinicalTrials.gov Identifier: NCT00013611     History of Changes
Obsolete Identifiers: NCT00002421
Other Study ID Numbers: 0303M44961
01-I-0126 ( Other Identifier: NIAID )
Study First Received: March 24, 2001
Results First Received: November 8, 2010
Last Updated: August 2, 2011
Health Authority: United States: Federal Government