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Trial record 46 of 178 for:    chlamydia infection | "Sexually Transmitted Diseases"

A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV (PREMISE)

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ClinicalTrials.gov Identifier: NCT03431168
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : March 20, 2018
Sponsor:
Information provided by (Responsible Party):
Jodie Dionne-Odom, University of Alabama at Birmingham

Brief Summary:
More than 3 billion people worldwide are at risk of acquiring malaria and pregnant women living with HIV in Africa are at particular risk. An effective prophylaxis regimen capable of preventing malaria and other common perinatal infections would have great potential to improve adverse birth outcomes. The purpose of this randomized controlled trial is to evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to determine its efficacy and safety.

Condition or disease Intervention/treatment Phase
HIV Pregnancy Malaria Sexually Transmitted Infection Drug: Azithromycin/TMPS Drug: Placebo/TMPS Phase 2

Detailed Description:

The World Health Organization (WHO) recommends malaria prophylaxis for all pregnant women living in endemic areas in order to reduce maternal anemia, low birth weight and perinatal mortality by 25-45%. The most commonly used regimen is intermittently dosed sulfadoxine-pyrimethamine (SP).Unfortunately, SP prophylaxis is contraindicated for HIV-infected pregnant women since co-administration with TMPS (trimethoprim-sulfamethoxazole) causes serious adverse events. TMPS (Bactrim or Cotrimoxazole) is an effective, well-tolerated, low-cost antibiotic that is used as prophylaxis in HIV-patients with low CD4 counts. It has anti-malarial activity with prophylactic efficacy that is comparable to SP (30-90%). Daily TMPS is recommended as malaria prophylaxis in pregnant women with HIV in many African countries (including Cameroon) but malaria infection rates are high even when medication compliance is excellent; thus, new and improved options are urgently needed. Azithromycin (AZ) is a macrolide antibiotic with activity against malaria, a good safety profile in pregnancy and proven utility as a part of combination malaria prevention regimens (such as SP-AZ). It also has activity against sexually transmitted infections (STI) and perinatal pathogens, including chlamydia (CT), gonorrhea (GC), syphilis and GBS (Streptococcus agalactiae or Group B Streptococcus), a potential but understudied contributor to high rates of newborn sepsis and death in Africa. SP-AZ prophylaxis in HIV-uninfected pregnant women has been reported to reduce prevalence of low birth weight (RR 0.74, 95% confidence interval (CI) 0.6-0.9) and preterm delivery (RR 0.66, 95% CI 0.48-0.91) compared to SP alone.

Thus, the central hypothesis is that a TMPS-AZ combination will be more effective than standard TMPS malaria prophylaxis in pregnant women with HIV, and that it will also decrease STI coinfection. Investigators plan a test-of-concept of the central hypothesis by conducting a double blinded, Phase II randomized controlled trial (RCT).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The PREMISE Trial: A Novel Regimen to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV
Actual Study Start Date : March 7, 2018
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Malaria

Arm Intervention/treatment
Active Comparator: Azithromycin/TMPS

Azithromycin 1 gm po daily x 3 days at enrollment and at each 4 week follow up visit.

TMPS double strength 1 tablet po daily.

Drug: Azithromycin/TMPS
2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
Other Name: Cotrimoxazole

Placebo Comparator: Placebo/TMPS

Azithromycin placebo 1 gm po daily x 3 days at enrollment and at each 4 week follow up visit.

TMPS double strength 1 tablet po daily.

Drug: Placebo/TMPS
2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
Other Name: Co-Trimoxazole




Primary Outcome Measures :
  1. Plasmodium falciparum peripheral parasitemia [ Time Frame: At end of pregnancy (>35 weeks) or at delivery ]
    P. falciparum detected by microscopy or polymerase chain reaction (PCR)

  2. Proportion with composite STI outcome [ Time Frame: will be measured in both groups (>35 weeks) or at delivery ]
    Including chlamydia (NAAT (nucleic acid amplification test) positive) , gonorrhea (NAAT positive), syphilis (non-treponemal and treponemal test positive) infections.


Secondary Outcome Measures :
  1. Mean infant birthweight [ Time Frame: at birth ]
    Neonatal weight measured with digital scale

  2. Proportion with adverse birth outcomes [ Time Frame: Birth outcomes will be measured at birth for all outcomes except early neonatal mortality defined as within 7 days of birth. Early neonatal mortality will be assessed at a six week follow up phone call. ]
    Composite measure: low infant birthweight (<2500 grams), miscarriage (<28 weeks), preterm delivery (<37 weeks), small for gestational age (SGA), congenital anomaly detected on surface examination, early neonatal mortality (within 7 days of birth)

  3. Maternal adherence to the prophylactic regimen [ Time Frame: Adherence will be documented from the date of randomization until the time of delivery, assessed up to 42 weeks. ]
    Directly observed therapy (DOT) in clinic for the 1st dose of study medication. Self-report and pill count will be used to assess adherence and maternal tolerability.

  4. Episodes of symptomatic malaria [ Time Frame: From the date of randomization until the time of delivery, assessed up to 42 weeks. ]
    Fever and positive malaria test (rapid diagnostic test) at routine visits or sick call visits or maternal report of malaria diagnosis.

  5. Mean geometric mean parasite density (GMPD) for Plasmodium falciparum [ Time Frame: At the end of pregnancy (>35 weeks gestational age (GA)) or at delivery ]
    Mean GMPD will be compared between the two study arms

  6. Proportion with placental malaria [ Time Frame: At delivery ]
    Placentas will be collected on a subset of women and impression smear will be used to assess for malaria infection

  7. Proportion with maternal anemia and severe maternal anemia [ Time Frame: At the end of pregnancy (>35 weeks) or at delivery ]
    anemia defined as hemoglobin <11 g/dL, severe anemia defined as hemoglobin <7 g/dL.

  8. Perinatal anogenital GBS colonization [ Time Frame: after 35 weeks GA or at delivery ]
    Proportion of women in each arm with GBS detected by NAAT

  9. Composite STI Measure (including all STI tests) [ Time Frame: After 35 weeks GA or at delivery ]
    Proportion of women with GC/CT (by NAAT), syphilis (by serology), Mycoplasma genitalium (NAAT).



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Ages Eligible for Study:   16 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed HIV-infection (documented in medical record)
  • Age ≥16 years
  • Confirmed pregnancy, <28 weeks estimated gestational age (by best obstetric estimate which may include ultrasound or fundal height and LMP)
  • Live singleton pregnancy
  • Receiving prenatal care at Mboppi Hospital or Mutengene Hospital
  • Plan to receive follow up prenatal care and deliver at study facility
  • Capable of providing written informed consent
  • Able and agree to come to facility for febrile episodes or acute illness during pregnancy (with reimbursement of transportation costs).
  • Agree to avoid antimalarial medications outside of study protocol.

Exclusion Criteria:

  • Severe anemia (last hemoglobin <6)
  • History of severe adverse reaction to co-trimoxazole or azithromycin
  • Active medical problem requiring inpatient evaluation at the time of screening
  • Intention of moving far away from the facility during pregnancy or not likely to return for follow up care or delivery
  • Signs or symptoms of early or active labor
  • History of severe cardiac disease (including congestive heart failure, severe valvular disease or arrhythmias).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03431168


Contacts
Contact: Jodie A Dionne-Odom, MD 205 975 6530 jdionne@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jodie Dionne-Odom    205-975-6530    jdionne@uabmc.edu   
Principal Investigator: Jodie A Dionne-Odom, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Jodie A Dionne-Odom, MD University of Alabama at Birmingham

Responsible Party: Jodie Dionne-Odom, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03431168     History of Changes
Other Study ID Numbers: IRB-300001112
First Posted: February 13, 2018    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jodie Dionne-Odom, University of Alabama at Birmingham:
STI Prevention
Cameroon
sub-Saharan Africa
HIV pregnancy
Malaria in pregnancy

Additional relevant MeSH terms:
Infection
Malaria
Sexually Transmitted Diseases
Protozoan Infections
Parasitic Diseases
Virus Diseases
Genital Diseases, Male
Genital Diseases, Female