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Protease Inhibitors to Reduce Malaria Morbidity in HIV-Infected Pregnant Women (PROMOTE-PIs)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00993031
First Posted: October 9, 2009
Last Update Posted: December 1, 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.
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Diana Havlir, University of California, San Francisco
Results First Submitted: January 5, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions: Malaria
HIV Infections
Interventions: Drug: Lopinavir/ritonavir
Drug: Efavirenz
Drug: Zidovudine
Drug: Lamivudine

  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
No text entered.

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
Without Protease Inhibitor

ZDV 300mg/3TC 150mg/EFV 600mg

Efavirenz: 600mg

Zidovudine: Zidovudine 300 mg

Lamivudine: Lamivudine 150 mg

With Protease Inhibitor

ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg

Lopinavir/ritonavir: LPV 200mg/r 50mg

Zidovudine: Zidovudine 300 mg

Lamivudine: Lamivudine 150 mg


Participant Flow:   Overall Study
    Without Protease Inhibitor   With Protease Inhibitor
STARTED   195   194 
Delivered   187   190 
COMPLETED   173   175 
NOT COMPLETED   22   19 
Death                0                1 
Physician Decision                0                2 
Withdrawal by Subject                3                3 
Lost to Follow-up                19                13 



  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
Without Protease Inhibitor

ZDV 300mg/3TC 150mg/EFV 600mg

Efavirenz: 600mg

Zidovudine: Zidovudine 300 mg

Lamivudine: Lamivudine 150 mg

With Protease Inhibitor

ZDV 300mg/3TC 150mg/LPV 200mg/r 50mg

Lopinavir/ritonavir: LPV 200mg/r 50mg

Zidovudine: Zidovudine 300 mg

Lamivudine: Lamivudine 150 mg

Total Total of all reporting groups

Baseline Measures
   Without Protease Inhibitor   With Protease Inhibitor   Total 
Overall Participants Analyzed 
[Units: Participants]
 195   194   389 
Age 
[Units: Years]
Mean (Standard Deviation)
 29.5  (5.4)   29.0  (5.4)   29.3  (7.6) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      195 100.0%      194 100.0%      389 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 
Gestational Age, wk 
[Units: Weeks]
Mean (Standard Deviation)
 21.1  (4.1)   21.2  (4.3)   21.1  (5.9) 
Previous Preganancies 
[Units: Participants]
     
 16   8   24 
 20   25   45 
≥2   159   161   320 
Bed Net Ownership 
[Units: Participants]
     
None   85   85   170 
Untreated   28   33   61 
ITN   77   70   147 
Yes; unknown treatment status   5   5   10 
Unknown   0   1   1 
Receiving TMP-SMX prophylaxis at enrollment [1] 
[Units: Participants]
 125   124   249 
[1] Trimethoprim/sulfamethoxazole (TMP-SMX) is an antibiotic used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole.
Hemoglobin level, g/dL 
[Units: g/dL]
Mean (Standard Deviation)
 10.9  (1.3)   11.0  (1.2)   10.9  (1.8) 
CD4+ T-cell count 
[Units: Cells/mm3]
Median (Inter-Quartile Range)
 374 
 (270 to 485) 
 368 
 (282 to 506) 
 370.5 
 (274 to 494) 
HIV RNA load 
[Units: Log10 copies/mL]
Median (Inter-Quartile Range)
 4.3 
 (3.5 to 4.8) 
 4.1 
 (3.3 to 4.7) 
 4.1 
 (3.4 to 4.8) 
WHO stage HIV disease [1] 
[Units: Participants]
     
 181   189   370 
 13   5   18 
 1   0   1 
 0   0   0 
[1] Stage 1=Asymptomatic; Stage 2= Moderate unexplained weight loss, Recurrent respiratory infections, Herpes zoster, Angular cheilitis, Recurrent oral ulceration, Papular pruritic eruptions, Seborrheic dermatitis, Fungal nail infections; Stage 3=Unexplained severe weight loss, Unexplained chronic diarrhea for >1 month, Unexplained persistent fever for >1 month, Persistent oral candidiasis, Oral hairy leukoplakia, Pulmonary tuberculosis, Severe presumed bacterial infections, Acute necrotizing ulcerative stomatitis, gingivitis, or periodontitis; Unexplained anemia; Stage 4 =HIV wasting syndrome,etc


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Prevalence of Malaria Defined as Positive Placental Blood Smear   [ Time Frame: Delivery ]

2.  Primary:   Prevalence of Malaria Defined as Positive Placental Blood PCR   [ Time Frame: Delivery ]

3.  Secondary:   Placental Malaria Defined as Positive Placental RDT   [ Time Frame: Delivery ]

4.  Secondary:   Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk During Pregnancy   [ Time Frame: Number of treatments given for clinical malaria based on postive blood smear from time from randomization until 24 months after delivery or cessation of breastfeeding ]

5.  Secondary:   Prevalence of Composite Clinical Outcome Defined by LBW, Stillbirth(Intrauterine Fetal Demise >20wks GA), Late Spontaneous Abortion(Miscarriage 12-20wks GA), Preterm Delivery(<37wks Gestation), Neonatal Death(Death of Liveborn Infant Within First 28days)   [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]

6.  Secondary:   Placental Malaria Defined Placental Histopathologic Analysis   [ Time Frame: Delivery ]

7.  Secondary:   Maternal Malaria Defined as the Number of Treatments for New Episodes of Malaria Per Time at Risk After Pregnancy   [ Time Frame: Number of treatments given for clinical malaria based on postive blood smear from time from delivery until 24 months after delivery or cessation of breastfeeding ]

8.  Secondary:   Prevalence of Severe Maternal Anemia Defined by Hemoglobin < 8g/dl at Any Point During the Trial in Each Treatment Group   [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]
Results not yet reported.   Anticipated Reporting Date:   12/2017  

9.  Secondary:   Incidence of Pre-eclampsia Defined by Hypertension > 140/90 on Two Occasions Measured > 6 Hours Apart With ≥1+ Proteinuria on Clean Catch Urine Dipstick   [ Time Frame: Time of randomization until 4 weeks postpartum ]
Results not yet reported.   Anticipated Reporting Date:   12/2017  

10.  Secondary:   Maternal HIV RNA Suppression of <400 Copies/mL and of <50 Copies/mL   [ Time Frame: At delivery and 24 weeks after the start of the treatment regimen ]
Results not yet reported.   Anticipated Reporting Date:   12/2017  

11.  Secondary:   Change in Maternal CD4 Cell Counts and % CD4   [ Time Frame: From ART initiation to delivery and from delivery to the cessation of breastfeeding ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

12.  Secondary:   Development of One or More New Maternal HIV Antiretroviral Resistance Mutations   [ Time Frame: Measured at delivery and 24 weeks postpartum. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

13.  Secondary:   Incidence of Maternal to Child Transmission of HIV, Measured by Infant HIV DNA PCR   [ Time Frame: From delivery to 24 weeks of life or the cessation of breastfeeding if that occurs prior to 24 weeks of life ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

14.  Secondary:   ART Levels in Plasma and Hair Samples   [ Time Frame: Women at 30-34 weeks gestation and 12 weeks postpartum; Infants at delivery, 12 weeks and 24 weeks of life. ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

15.  Secondary:   Prevalence of Grade 3 or 4 Toxicity at Any Point During the Trial in the Two Treatment Groups in Women and in Infants   [ Time Frame: Time from randomization until 24 months postpartum or cessation of breastfeeding ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  


  Serious Adverse Events


  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
A semi-immune population of adults at relatively low risk for malaria; a high rate of TMP-SMX prophylaxis ; A lower than expected incidence of malaria, resulting in the possibility that the study was underpowered


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Results Point of Contact:  
Name/Title: Diane V Havlir, MD
Organization: University of California, San Francisco
phone: 01-415-476-4082 ext 400
e-mail: dhavlir@php.ucsf.edu


Publications of Results:

Other Publications:

Responsible Party: Diana Havlir, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00993031     History of Changes
Other Study ID Numbers: H5741-34342
P01HD059454 ( U.S. NIH Grant/Contract )
2009-141 ( Other Identifier: Makerere Univ Fac of Med Research and Ethics Committee )
HS-670 ( Other Identifier: Uganda National Council for Science and Tech )
592/ESR/NDA/DID-09/2009 ( Other Identifier: Uganda National Drug Authority )
H5741-34342 and 10-02958 ( Other Identifier: UCSF Committee on Human Research )
First Submitted: October 8, 2009
First Posted: October 9, 2009
Results First Submitted: January 5, 2015
Results First Posted: December 1, 2017
Last Update Posted: December 1, 2017