PEPPER-trial

2023-507763-18-01 Therapeutic use (Phase IV) Ongoing, recruiting

Start 21 May 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 9 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 142
Countries 1
Sites 9

Placenta previa, preterm birth

1. To assess the effectiveness of progesterone - started between 18- and 24-weeks of gestation, compared to no treatment - in the prevention of preterm birth in women with a placenta previa. We will assess total preterm birth rates and rates subdivided in spontaneous and iatrogenic preterm birth at different gestationa…

Key facts

Sponsor
Amsterdam UMC
Participant type
Pediatric, Patients
Age range
In Utero, 0-17 years, 18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
21 May 2024 → ongoing
Decision date (initial)
2024-02-16
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes

External identifiers

EU CT number
2023-507763-18-01
WHO UTN
U1111-1295-4225

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis

1. To assess the effectiveness of progesterone - started between 18- and 24-weeks of gestation, compared to no treatment - in the prevention of preterm birth in women with a placenta previa. We will assess total preterm birth rates and rates subdivided in spontaneous and iatrogenic preterm birth at different gestational age cut-offs, duration of pregnancy, neonatal mortality and morbidity, and maternal side effects. 2. The primary outcome measure will be the relative risk of preterm birth before 37 weeks of gestation.

Secondary objectives 1

  1. Secondary outcomes will be the relative risk of preterm birth before 34 weeks of gestation, and preterm births will also be assessed as spontaneous and indicated separately for different cut-offs (28, 32, 34 and 37 weeks of gestation). Neonatal outcomes will be a composite adverse neonatal outcome for neonatal morbidity and neonatal mortality, and components will also be assessed separately. Maternal outcomes will be maternal morbidity and side effects, and (indication for chosen) mode of birth.

Conditions and MedDRA coding

Placenta previa, preterm birth

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Intervention group
Study participants in the intervention arm will be treated with 200 mg Utrogestan, once daily, ante noctem. The study medication (Utrogestan) will not be labeled.
Randomised Controlled None Control group: The control group will receive expectant management as is currently standard practice.

Regulatory references

EU CT numberTitleSponsor
2023-507763-18-00 Progesterone for prEventing Preterm births in women with PlacEnta pRevia (PEPPER-trial) Amsterdam UMC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. Women pregnant of a singleton – without any other high-risk factor for preterm birth - diagnosed with a placenta previa diagnosed between 18- and 24 weeks of gestation.

Exclusion criteria 1

  1. 1. Multiple pregnancy, 2. Major fetal congenital and/or chormosomal abnormalities, 3. Cervical cerclage or pessary in situ or planned to be placed, 4. Cervical dilation ≥ 3cm, 5. Intra-uterine fetal death, 6. Women with an already existing indication for progesterone use per current guidelines, 7. (Suspected) placenta accreta spectrum disorder, 8. Contra-indication for progesterone use, 9. Inability to give informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Number of PTB before 37 weeks of gestation

Secondary endpoints 1

  1. 1. sPTB/iPTB <37wks, 2. PTB >24wks, 3. Total PTB, sPTB, iPTB <28/32/34wks, 4. Mean gestational age, 5. Incidence of <10th/3rd percentile birthweight, 6. Umbilical cord blood pH (arterial/venous), 7. Apgar <7 at 5 mins, 8. NICU admissions (>24 hrs, hrs in NICU), 9. Components of composite outcome, 10. Planned/unplanned CS, 11. Admission for antenatal blood loss (incidence), 12. Threatened preterm birth (incidence).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Progesterone

SCP145363 · ATC

Active substance
Progesterone
Route of administration
VAGINAL USE
Max daily dose
200 mg milligram(s)
Max total dose
25200 mg milligram(s)
Max treatment duration
18 Week(s)
Authorisation status
Authorised
ATC code
G03DA04 — PROGESTERONE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation
Amsterdam UMC
Address
De Boelelaan 1117
City
Amsterdam
Postcode
1081 HV
Country
Netherlands

Scientific contact point

Organisation
Amsterdam UMC
Contact name
Prof. Dr. E. Pajkrt

Public contact point

Organisation
Amsterdam UMC
Contact name
Prof. Dr. E. Pajkrt

Locations

1 EU/EEA country · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 142 9
Rest of world 0

Investigational sites

Netherlands

9 sites · Ongoing, recruiting
Noordwest Ziekenhuisgroep Stichting
Gynaecology, Wilhelminalaan 12, 1815 JD, Alkmaar
OLVG Stichting
Gynaecology, Oosterpark 9, 1091 AC, Amsterdam
Rode Kruis Ziekenhuis B.V.
Gynaecology, Vondellaan 13, 1942 LE, Beverwijk
Flevoziekenhuis Stichting
Gynaecology, Hospitaalweg 1, 1315 RA, Almere
Dijklander Ziekenhuis
Gynaecology, Maelsonstraat 3, 1624 NP, Hoorn Nh
Zaans Medisch Centrum Stichting
Gynaecology, Koningin Julianaplein 58, 1502 DV, Zaandam
Academisch Medisch Centrum
Gynaecology, Meibergdreef 9, 1105 AZ, Amsterdam
Spaarne Gasthuis
Gynaecology, Spaarnepoort 1, 2134 TM, Hoofddorp
Tergooiziekenhuizen
Gynaecology, Van Riebeeckweg 212, 1213 XZ, Hilversum

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2024-05-21 2024-05-21

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-10-26 Netherlands Acceptable
2024-02-16
2024-02-16
2 NON SUBSTANTIAL MODIFICATION NSM-1 2024-03-14 Netherlands Acceptable
2024-02-16
2024-03-14
3 SUBSTANTIAL MODIFICATION SM-1 2024-05-28 Netherlands Acceptable 2024-06-26