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PneumoniaPhase 3PROPELNCT02628886

Protecting From Pneumococcus in Early Life (The PROPEL Trial)

A Phase 3 study testing 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid and tetanus toxoid in people with Pneumonia, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for
Pneumonia
What is being tested?
13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid and tetanus toxoid
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
600 participants
Where
1 siteThe Gambia
Study dates
11 Mar 2016to Dec 2020
Phase
Phase 3
Are there results?
None posted in the registry

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 18 to 40 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

The Gambia1 site
  • Sukuta Health Centre

    Banjul

Other trials in The Gambia

About this study

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

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.

Read more

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.

Read the detailed description

Members of the clinical trial team will base themselves within the government run antenatal clinics at the clinical trial sites in order to identify potentially eligible pregnant women. Working closely alongside government midwifery and nursing staff they will aim to identify pregnant women who are yet to reach 34 weeks gestation and who are thus potentially eligible for enrolment. Assessment of gestation at this first contact point will be based on the date of the LMP or the assessment of fundal height as is local practice (gestational age will be confirmed by ultrasound scanning once informed consent has been obtained and ultrasound based assessment will be used to determine final eligibility).

A member of the clinical trial team will discuss the study with potentially eligible expectant mothers who are provisionally interested and agree to receive this additional information. The discussion will be based on the contents of the informed consent document (ICD) and a copy of the ICD will be provided to the expectant mother at the end of the discussion.

Potentially eligible women who are interested will be encouraged to discuss the study with their spouse and other family members as appropriate. Following individual sensitization of the mother, a member of the field team may provide information to other family members (particularly the spouse) either by telephone or through a visit to the subject's residence according to the preference of the mother.

Expectant mothers who express an interest in participation will then be contacted to arrange a visit to the clinical trial site where informed consent will be undertaken. Written/thumb-printed informed consent will only be required from the expectant mother but in all cases it will be confirmed directly with the spouse (the father of the unborn baby) that they are aware of the study and have given their agreement. In the case of expectant mothers who are literate in English, they will be provided with a copy of the ICD but a member of the clinical trial team will nonetheless review the contents of the ICD line by line in English to ensure all details are covered and that the subject has the opportunity to ask questions regarding any aspect of the trial.

In the case of potential participants who are not literate in English but only in one of the local languages, a member of the clinical trial team fluent in the local language (as well as being English literate) will review the ICD line by line translating directly from the English ICD to the appropriate local language. In this case an impartial witness must be present throughout all elements of the consent process and must attest that the information on the ICD has been given accurately and in full. The impartial witness will also be required to sign the ICD to confirm that this has been the case.

Informed consent for study participation will be documented on the signature page of the ICD. The option to consent for the future use of any residual samples on study completion will also be given on the same page but the provision of such additional consent is not required for participation in the main trial.

A certified copy of the ICD is provided to the participant unless it is refused for some reason in which case it will be filed at the trial site. Such refusal must be documented in the subject's file so it is clear that the subject has been offered a copy The study will randomize 600 pregnant women at between 28 and 34 weeks gestation. Mothers will not be replaced following randomization. Screening of potentially eligible women will continue until this number is reached unless the trial is stopped for some other reason.

No further selection or assessment of eligibility will be undertaken on the newborn infants. All data will be included in the safety reporting irrespective of pregnancy outcome and safety follow-up should occur as planned for all infants. An infant may be excluded from the trial for the purposes of vaccination and/or clinical sampling if ongoing participation is considered to be against their best interests or if a contraindication to vaccination and/or to the obtaining of clinical samples is identified. An infant excluded in this way would not be replaced and hence this would not alter the target sample size of 600 pregnant women.

Conditions
Pneumonia
Being tested
13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid, placebo 0.9% sodium chloride plus tetanus toxoid, tetanus toxoid
Keywords
maternal and neonatal pneumococcal conjugate vaccination, pneumococcal carriage
Medical subject headings
Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoidBiological

    Also called PCV13

    pregnant women will be given intramuscular PCV 13 vaccine between 28-34 weeks

  • placebo 0.9% sodium chloride plus tetanus toxoidBiological

    Also called placebo

    pregnant women will be given intramuscular saline injection between 28-34 weeks

  • tetanus toxoidOther

    new born babies will be given PCV13 vaccine at birth

Study groups in NCT02628886
Study groupRoleWhat they receive
maternal groupExperimental13-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
Receives: Biological: 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid
control groupPlacebo comparatorplacebo 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
Receives: Biological: placebo 0.9% sodium chloride plus tetanus toxoid
neonatal groupExperimentaltetanus toxoid to pregnant women between 28-34 weeks and their infants will get PCV 13 0.5ml at birth, 8 weeks and 16 weeks
Receives: Other: tetanus toxoid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. safety in pregnant mothers (SAE)

    SAE in expectant mothers from enrollment at 28 to 34 weeks gestation up to eight weeks from the end of the pregnancy

    Measured: from 28 weeks gestation to 8 weeks after delivery

  2. safety in newborns (SAE)

    SAE in infants from birth until nine months of age

    Measured: from birth until nine months of age

  3. safety in vaccinated pregnant women (local and systemic reactogenicity)

    Local and systemic reactogenicity within the first seven days of PCV13 administration to expectant mothers at between 28 and 34 weeks gestation

    Measured: within the first seven days from vaccination

  4. safety in vaccinated newborns (local and systemic reactogenicity)

    Local and systemic reactogenicity within the first seven days of PCV13 administration to newborn infants within the first week of life

    Measured: within the first seven days from vaccination

  5. outcome of pregnancy

    Pregnancy outcome

    Measured: from 28 weeks of gestation to delivery

  6. cumulative carriage acquisition rate in infants

    collection of Naso Pharyngeal Swab to assess Vaccine Type (VT) pneumococcal carriage rate

    Measured: from birth to 20 weeks of age

Secondary outcomes (7)
  1. pneumococcal nasopharyngeal carriage rate of pregnant women

    Nasopharyngeal carriage rate of total and VT pneumococcus in the mothers at delivery and at eight weeks following delivery

    Measured: at delivery and at 8 weeks after delivery

  2. nasopharyngeal carriage rate of infants

    Nasopharyngeal carriage rate of total and VT pneumococcus in infants up to nine months of age

    Measured: form birth 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

    quantitative antibodies measurements and sero protection rate for both mothers and infants

    Measured: at delivery and 8 weeks post delivery for the mothers and for the infants at birth, 8 weeks, 20 weeks and 9 months

  4. opsonophagocytic antibodies titres in infants

    qualitative antibodies measurements in infants

    Measured: at birth, 8 & 20 weeks of age

  5. polio virus type 1,2,3, Geometric Mean Titre (GMT) and hepatitis B GMC sero protection rate in infants

    effect of co-administration of PCV13 with polio and hepatitis B vaccines

    Measured: at 8 weeks of age

  6. diptheria toxoid GMC sero protection rate

    the effect of the diptheria mutant carrier protein on subsequent vaccination to the infants

    Measured: at birth, 8 & 20 weeks of age

  7. tetanus toxoid GMC sero protection rate in mothers

    effect of co-administration with PCV13

    Measured: at birth

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2015 (estimated)
  2. Study start11 Mar 2016
  3. Primary completion19 Feb 2019
  4. Study completionDec 2020 (estimated)

Resources

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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02628886
Sponsor's protocol ID
SCC 1433
Acronym
PROPEL
Status last verified
Oct 2020
First submitted
7 Dec 2015
Last updated
23 Oct 2020
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 13-valent pneumococcal conjugate vaccine [Prevenar13®] plus tetanus toxoid and tetanus toxoid in people with Pneumonia, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.

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 7 inclusion and 26 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: status not confirmed, as of the sponsor's last update on 23 Oct 2020. 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 The Gambia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

safety in pregnant mothers (SAE) (time frame: from 28 weeks gestation to 8 weeks after delivery). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 23 Oct 2020.

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