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Protecting From Pneumococcus in Early Life (The PROPEL Trial) (PROPEL)

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ClinicalTrials.gov Identifier: NCT02628886
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : February 27, 2019
Sponsor:
Collaborators:
WHO Pneumococcal Serology Reference Laboratory Institute of Child Health
BUGS Bioscience London Bioscience Innovation Centre 2 Royal College Street London
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

Streptococcus pneumoniae is responsible for over 10 percent of death in children under five and many of these deaths occur in early infancy before the current pneumococcal schedule is effective and nearly half occur in sub Saharan Africa.

The PROPEL trial will examine the effect of either a maternal or a neonatal dose of a pneumococcal conjugate vaccine on pneumococcal colonisation in the nose which can be used to measure the risk of disease in early life.

600 Expectant mothers will be randomized at between 28 and 34 weeks to a maternal group, a neonatal group or a control group in equal number (200 per group). Their subsequent born offspring will be followed up until nine months of age. Infants born from expectant mothers in the maternal and control group will receive their subsequent pneumococcal conjugate vaccination according to the national Expanded Programme on Immunisation (EPI) schedule in the Gambia at 8, 12 and 16 weeks while infants born to expectant mothers in the control group will receive the pneumococcal conjugate vaccine within 48 hours of birth and at 8 and 16 weeks of life. Randomization will be undertaken by defined un-blinded members of the clinical trial team who will be delegated for this task and who will not be involved in any other trial related procedures Pregnant women who are willing and who are identified by the staff of the government antenatal clinic as being potentially eligible according to gestation (assessed initially according to the date of the last menstrual period (LMP) - if known, or the fundal height), will be referred to a member of the clinical trial team.

Those who remain interested in participation having had the details of the study explained will have basic demographic, obstetric and contact details collected and will be invited, at a time of their convenience, to the Medical Research Council (MRC) clinical trial site for the formal informed consent process to be completed. Following informed consent, pregnancy will be confirmed with a urinary pregnancy test. Initial screening (e.g. for past-obstetric history and past-medical history etc) will be undertaken at this point along with screening bloods for serology (HIV, hepatitis B and syphilis) and haematology (haemoglobin and sickle test). A dating ultrasound scan (USS) will also be undertaken by designated clinical trial staff. On completion of screening, expectant mothers who are confirmed to be eligible according to the defined inclusion and exclusion criteria will be enrolled and randomized in parallel into one of three equally sized groups mentioned above (maternal, neonatal, control).

According to the group into which they have been randomized, mothers will receive a dose of PCV13 and tetanus toxoid [maternal group], placebo (0.9% sodium chloride) and tetanus toxoid [control group] or tetanus toxoid alone [neonatal group]. From this point on, the maternal and control groups (now 'Routine EPI Schedule') will be followed up in exactly the same way for the purposes of interventions and all endpoint assessments. Infants in the neonatal group ('Neonatal Schedule') will be followed up according to the schedule outlined.

At the time of presentation to the delivery unit a blood sample for serology and malaria Rapid Diagnostic Test (RDT) and an nasopharyngeal swab (NPS) sample will be obtained prior to or shortly following delivery. Immediately following delivery a sample of cord blood will be obtained and as soon as possible an NPS sample will be taken from the newborn. Anthropometric measurements will be taken from the newborn and an examination conducted. Once there has not been any contraindication to vaccination identified, all newborns will be administered the routine EPI vaccines according to the schedule in The Gambia (BCG, Hepatitis B and OPV). Those newborns in the Neonatal group will additionally be administered a single intramuscular (IM) dose of PCV13. At two, three and four months, infants will be administered the routine EPI vaccines. Those infants in the Maternal and Control Groups (Routine EPI Schedule) will additionally receive PCV13 at eight, 12, and 16 weeks while those in the Neonatal group will receive the vaccine at eight and 16 weeks only having received the first dose at birth. All infants will additionally receive a single dose of the inactivated poliovirus vaccine (IPV) at 16 weeks in line with the routine EPI schedule in The Gambia.

Following the vaccines administered to expectant mothers and following the vaccines administered at birth, home visits will be undertaken on day 1 to 6 to collect solicited local and systemic adverse (for PCV only) reactions and any unsolicited. A day 7 safety clinic visit will be conducted following the vaccines administered to expectant mothers and following the vaccines administered at birth. Infant will attend the clinical trial site for NPS and blood samples to be taken at specific time points.


Condition or disease Intervention/treatment Phase
Pneumonia Biological: 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid Biological: placebo 0.9% sodium chloride plus tetanus toxoid Other: tetanus toxoid Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Controlled, Double-blind, Phase 3 Trial to Evaluate the Effects of Maternal or Neonatal Pneumococcal Conjugate Vaccination on Pneumococcal Carriage in Infants up to Nine Months of Age - The PROPEL Trial
Actual Study Start Date : March 11, 2016
Actual Primary Completion Date : February 19, 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia Tetanus

Arm Intervention/treatment
Experimental: maternal group
13-valent pneumococcal conjugate vaccine [Prevenar13®] (PCV13) vaccine, 0.5ml, once, stat, plus tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV13 at 8, 12 and 16 weeks according to normal EPI vaccination in country
Biological: 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid
pregnant women will be given intramuscular PCV 13 vaccine between 28-34 weeks
Other Name: PCV13

Placebo Comparator: control group
placebo sterile 0.9% sodium chloride, 0.5ml, once, stat plus tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV13 at 8, 12 and 16 weeks according to normal EPI vaccination in country
Biological: placebo 0.9% sodium chloride plus tetanus toxoid
pregnant women will be given intramuscular saline injection between 28-34 weeks
Other Name: placebo

Experimental: neonatal group
tetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV 13 0.5ml at birth, 8 weeks and 16 weeks
Other: tetanus toxoid
new born babies will be given PCV13 vaccine at birth




Primary Outcome Measures :
  1. safety in pregnant mothers (SAE) [ Time Frame: from 28 weeks gestation to 8 weeks after delivery ]
    SAE in expectant mothers from enrollment at 28 to 34 weeks gestation up to eight weeks from the end of the pregnancy

  2. safety in newborns (SAE) [ Time Frame: from birth until nine months of age ]
    SAE in infants from birth until nine months of age

  3. safety in vaccinated pregnant women (local and systemic reactogenicity) [ Time Frame: within the first seven days from vaccination ]
    Local and systemic reactogenicity within the first seven days of PCV13 administration to expectant mothers at between 28 and 34 weeks gestation

  4. safety in vaccinated newborns (local and systemic reactogenicity) [ Time Frame: within the first seven days from vaccination ]
    Local and systemic reactogenicity within the first seven days of PCV13 administration to newborn infants within the first week of life

  5. outcome of pregnancy [ Time Frame: from 28 weeks of gestation to delivery ]
    Pregnancy outcome

  6. cumulative carriage acquisition rate in infants [ Time Frame: from birth to 20 weeks of age ]
    collection of Naso Pharyngeal Swab to assess Vaccine Type (VT) pneumococcal carriage rate


Secondary Outcome Measures :
  1. pneumococcal nasopharyngeal carriage rate of pregnant women [ Time Frame: at delivery and at 8 weeks after delivery ]
    Nasopharyngeal carriage rate of total and VT pneumococcus in the mothers at delivery and at eight weeks following delivery

  2. nasopharyngeal carriage rate of infants [ Time Frame: form birth up to nine months of age ]
    Nasopharyngeal carriage rate of total and VT pneumococcus in infants up to nine months of age

  3. pneumococcal vaccine type specific Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) and sero protection rates in mothers and infants [ Time Frame: at delivery and 8 weeks post delivery for the mothers and for the infants at birth, 8 weeks, 20 weeks and 9 months ]
    quantitative antibodies measurements and sero protection rate for both mothers and infants

  4. opsonophagocytic antibodies titres in infants [ Time Frame: at birth, 8 & 20 weeks of age ]
    qualitative antibodies measurements in infants

  5. polio virus type 1,2,3, Geometric Mean Titre (GMT) and hepatitis B GMC sero protection rate in infants [ Time Frame: at 8 weeks of age ]
    effect of co-administration of PCV13 with polio and hepatitis B vaccines

  6. diptheria toxoid GMC sero protection rate [ Time Frame: at birth, 8 & 20 weeks of age ]
    the effect of the diptheria mutant carrier protein on subsequent vaccination to the infants

  7. tetanus toxoid GMC sero protection rate in mothers [ Time Frame: at birth ]
    effect of co-administration with PCV13



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed/thumb-printed informed consent for trial participation obtained*
  • Pregnant woman aged between 18 and 40 years of age inclusive10*
  • Singleton pregnancy*
  • From 28 to 34 weeks11 gestation as determined by USS
  • Resident within easy reach of the clinical trial site (no fixed boundaries will be set and such judgements will be made on a case by case basis by members of the field team in discussion with the potential participant, taking into account knowledge of the local transport links and geography)*
  • Intention to deliver at the health centre related to the clinical trial site (i.e. Sukuta and Faji Kunda health centres)*
  • Willingness and capacity to comply with all the study procedures, including those relating to the newborn infant, in the opinion of the principal investigator or designee

Exclusion Criteria:

  • History of pre-eclampsia or eclampsia
  • History of gestational diabetes
  • Previous late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation)
  • Previous premature delivery (defined as delivery before 37 weeks gestation)
  • Previous neonatal death (defined as death of an infant within the first 28 days of life)
  • Previous Caesarean section
  • Previous delivery of an infant with major congenital anomalies
  • Previous delivery of an infant with a known or suspected genetic or chromosomal abnormality
  • History of other significant pregnancy related complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected
  • History of other significant neonatal complications judged likely to affect the safety of the mother or infant or to significantly compromise the endpoint data collected
  • Significant complications in current pregnancy
  • Significant alcohol consumption during current pregnancy
  • Significant maternal chronic illness including but not limited to hypertension requiring treatment, heart disease, lung disease, neurological disorders including a history of epilepsy or recurrent afebrile seizures, kidney disease, liver disease, anaemia and other haematological disorders, endocrine disorders including known diabetes mellitus, autoimmunity
  • Severe anaemia (<7.0g/dL)[51]
  • Known Human Immunodeficiency Virus (HIV) or hepatitis B (HBV) virus positive or found to be HIV or HBV positive during screening
  • Positive result for syphilis infection on laboratory testing
  • Known prior receipt of a pneumococcal vaccine (pneumococcal conjugate or pneumococcal polysaccharide vaccine)
  • Receipt of any vaccine during the current pregnancy or plans to receive any non-study vaccines during the current pregnancy (tetanus toxoid vaccination is not an exclusion and vaccines given during national campaigns if applicable will not generally be exclusions)
  • Any other condition judged to significantly increase the risks to either the mother or the infant within the current (including relevant history from previous pregnancies
  • History of anaphylactic or severe allergic reactions to previous vaccines or history of anaphylactic or severe allergic reactions in previous offspring (if applicable)
  • Receipt of any blood product including human immunoglobulins at any stage during the current pregnancy or plan to receive any blood products during the period or trial participation (receipt or blood products in an emergency or for obstetric reasons will not represent a protocol deviation given such situations are unplanned)
  • Receipt of immunosuppressive or immuno-modulatory medication at any stage during the current pregnancy or plan to receive any such medication during the period or trial participation
  • Clinically suspected or confirmed congenital or acquired clotting or bleeding disorders or the current receipt of medications known to alter clotting or bleeding
  • Current malaria infection (on the day of randomization and vaccination)
  • Any clinically significant signs or symptoms of acute illness, significant abnormalities in vital signs, an axillary temperature of > 37.5°C or any recorded fever (> 37.5°C) in the preceding 24 hours.
  • 2 or more symptoms (nausea/vomiting, diarrhoea, headaches, fatigue and myalgia) rated as grade 2 and clinically significant on the maternal systemic reactogenicity scale present at baseline on the day of vaccination

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): NCT02628886


Locations
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Gambia
Sukuta Health Centre
Banjul, Gambia
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
WHO Pneumococcal Serology Reference Laboratory Institute of Child Health
BUGS Bioscience London Bioscience Innovation Centre 2 Royal College Street London
Investigators
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Principal Investigator: Ed Clarke, MB Medical Research Council Unit, The Gambia

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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT02628886     History of Changes
Other Study ID Numbers: SCC 1433
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019
Keywords provided by London School of Hygiene and Tropical Medicine:
maternal and neonatal pneumococcal conjugate vaccination
pneumococcal carriage
Additional relevant MeSH terms:
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Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs