HIVPhase 2PREMISENCT03431168
A Novel Regimen to Prevent Malaria and STI in Pregnant Women With HIV
A Phase 2 study testing Azithromycin/TMPS in people with HIV and Pregnancy Malaria, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 55 years, women only
- Conditions the study is for
- HIV, Pregnancy Malaria, Sexually Transmitted Infection
- What is being tested?
- Azithromycin/TMPS
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 308 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2018to 1 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 55 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: The PREMISE Trial: A Novel Regimen to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV
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.
Read the 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).
- Conditions
- HIV, Pregnancy Malaria, Sexually Transmitted Infection
- Being tested
- Azithromycin/TMPS, Placebo/TMPS
- Keywords
- STI Prevention, Cameroon, sub-Saharan Africa, HIV pregnancy, Malaria in pregnancy
- Medical subject headings
- Sexually Transmitted Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin/TMPSDrug
Also called Cotrimoxazole
2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
Placebo/TMPSDrug
Also called Co-Trimoxazole
2 tabs po daily x 3 days at enrollment and at each monthly follow up visit
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin/TMPS | Active comparator | 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. Receives: Drug: Azithromycin/TMPS |
| Placebo/TMPS | Placebo comparator | 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. Receives: Drug: Placebo/TMPS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasmodium Falciparum Peripheral Parasitemia
- falciparum detected by microscopy or polymerase chain reaction (PCR)
Measured: At end of pregnancy (>35 weeks) or at delivery
Proportion With Composite STI Outcome
Including chlamydia (NAAT (nucleic acid amplification test) positive) , gonorrhea (NAAT positive), syphilis (non-treponemal and treponemal test positive) infections.
Measured: will be measured in both groups (>35 weeks) or at delivery
Secondary outcomes (8)
Low Birthweight (<2500 Grams)
Neonatal weight measured with digital scale
Measured: at birth
Proportion With Adverse Birth Outcomes
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)
Measured: 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.
Maternal Adherence to the Prophylactic Regimen
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 for study medications taken at home from the time of enrollment until delivery. At each follow up visit and at delivery, participants will complete a medication adherence survey. They will self-report adherence to the 3 day study regimen (AZ or placebo).
Measured: Adherence of study medication taken at home will be documented from the date of randomization until the time of delivery, assessed up to 42 weeks.
Proportion of Participants With Symptomatic Malaria
Fever and positive malaria test (rapid diagnostic test) at routine visits or sick call visits or maternal report of malaria diagnosis.
Measured: From the date of randomization until the time of delivery, assessed up to 42 weeks.
Proportion With Placental Malaria
Placentas will be collected on a subset of women and impression smear will be used to assess for malaria infection
Measured: At delivery
Proportion With Maternal Anemia and Severe Maternal Anemia
anemia defined as hemoglobin <11 g/dL, severe anemia defined as hemoglobin <7 g/dL.
Measured: At the end of pregnancy (>35 weeks) or at delivery
Composite STI Measure (Including All STI Tests)
Proportion of women with GC/CT (by NAAT), syphilis (by serology), Mycoplasma genitalium (NAAT).
Measured: After 35 weeks GA or at delivery
GBS Colonization
anogenital GBS colonization detected by NAAT (PCR)
Measured: at or near term or at delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2018
- Study start7 Mar 2018
- Primary completion1 Jan 2021
- Study completion1 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 308 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jodie A. Dionne, MD, University of Alabama at Birmingham
- Investigators
- Jodie A Dionne-Odom, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03431168
- Sponsor's protocol ID
- IRB-300001112
- Acronym
- PREMISE
- Status last verified
- Nov 2023
- First submitted
- 2 Jan 2018
- Last updated
- 27 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.
PubMed 39324693
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The PREMISE Trial: A Novel Regimen to Prevent Malaria and Sexually Transmitted Infections in Pregnant Women With HIV
- ClinicalTrials.gov ID
- NCT03431168
- Acronym / sponsor ID
- PREMISE / IRB-300001112
- Conditions
- HIV, Pregnancy Malaria, Sexually Transmitted Infection
- Keywords
- STI Prevention, Cameroon, sub-Saharan Africa, HIV pregnancy, Malaria in pregnancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 308 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 7 Mar 2018 (actual)
- Primary completion
- 1 Jan 2021 (actual)
- Study completion
- 1 Jan 2022 (actual)
- First posted
- 13 Feb 2018 (actual)
- Results
- Posted 4 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin/TMPS | Active comparator | Drug: Azithromycin/TMPSAzithromycin 1 gm po daily x 3 days at enrollment and at each 4 week follow up visit. TMPS double strength 1 tablet po daily. |
| Placebo/TMPS | Placebo comparator | Drug: Placebo/TMPSAzithromycin 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. |
Who may qualify
- Ages
- 16 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin/TMPSAlso: Cotrimoxazole2 tabs po daily x 3 days at enrollment and at each monthly follow up visit | Drug | Azithromycin/TMPS |
| Placebo/TMPSAlso: Co-Trimoxazole2 tabs po daily x 3 days at enrollment and at each monthly follow up visit | Drug | Placebo/TMPS |
Primary outcome
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)
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.
8 secondary outcomes
Low Birthweight (<2500 Grams)
Time frame: at birth
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.
Maternal Adherence to the Prophylactic Regimen
Time frame: Adherence of study medication taken at home will be documented from the date of randomization until the time of delivery, assessed up to 42 weeks.
Proportion of Participants With Symptomatic Malaria
Time frame: From the date of randomization until the time of delivery, assessed up to 42 weeks.
Proportion With Placental Malaria
Time frame: At delivery
Proportion With Maternal Anemia and Severe Maternal Anemia
Time frame: At the end of pregnancy (>35 weeks) or at delivery
Composite STI Measure (Including All STI Tests)
Time frame: After 35 weeks GA or at delivery
GBS Colonization
Time frame: at or near term or at delivery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39324693Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jodie A Dionne-Odom, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azithromycin/TMPS in people with HIV and Pregnancy Malaria, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasmodium Falciparum Peripheral Parasitemia (time frame: At end of pregnancy (>35 weeks) or at delivery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03431168, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2023.