PREMI trial

2023-503220-76-01 Protocol LUMC-PREMI Therapeutic use (Phase IV) Ongoing, recruiting

Start 13 Feb 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 12 sites · Protocol LUMC-PREMI

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ongoing, recruiting
Participants planned 490
Countries 1
Sites 12

Unexplained recurrent miscarriages

The primary aim of the PREMI trial is to assess the effect of prednisolone administration during early pregnancy in women with unexplained recurrent miscarriages in comparison to the use of a placebo, specifically focusing on the live birth rate as the primary outcome measure.

Key facts

Sponsor
Leiden University Medical Center
Participant type
Patients
Age range
18-64 years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
13 Feb 2024 → ongoing
Decision date (initial)
2023-10-05
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
ZonMw

External identifiers

EU CT number
2023-503220-76-01
ClinicalTrials.gov
NCT05725512

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary aim of the PREMI trial is to assess the effect of prednisolone administration during early pregnancy in women with unexplained recurrent miscarriages in comparison to the use of a placebo, specifically focusing on the live birth rate as the primary outcome measure.

Secondary objectives 3

  1. Ongoing pregancy rate
  2. Miscarriage rate
  3. Evaluate side-effects and adverse events (congenital birth defects, low birth-weight, maternal side-effects etc.)

Conditions and MedDRA coding

Unexplained recurrent miscarriages

VersionLevelCodeTermSystem organ class
21.1 LLT 10038104 Recurrent abortion 10036585

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Prednisolone administration in women with REcurrent MIscarriages
Start inclusion; fall 2023 Inclusion duration 30 months Follow-up period 12 months per subject after randomization of intervention
 Randomised Controlled Double [{"id":89087,"code":5,"name":"Carer"},{"id":89086,"code":1,"name":"Subject"},{"id":89085,"code":2,"name":"Investigator"},{"id":89088,"code":4,"name":"Analyst"}] Prednisolone: 245 subjects will be randomised to this arm
Placebo: 245 subjects will be randomised to this arm

Regulatory references

Plan to share IPD
No
IPD plan description
This is a substantial modifiction, we as a research group have not yet discussed the sharing of IPD. It is most likely that we will share IPD.
EU CT numberTitleSponsor
2023-503220-76-00 Prednisolone administration in women with unexplained REcurrent MIscarriages Leiden University Medical Center

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. Age 18-39
  2. Two or more miscarriages (mola and ectopic pregnancies excluded)
  3. No underlying cause was found for miscarriages after examination

Exclusion criteria 7

  1. Diabetes with medication
  2. Previous enrollment/ participation in PREMI trial
  3. Contraindication for the use of glucocorticosteroids
  4. Use of medication that interferes with prednisolone (see protocol for list)
  5. Instable or exacerbation of auto-immune disease
  6. Use of immune suppressing medication (for any reason)
  7. Participation or enrollment in other interventional trial for recurrent miscarriages

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Last study subject has completed last visit and all data is gathered

Secondary endpoints 1

  1. DSMB advises to stop trial (for feasibility, slow inclusion rate, safety concerns etc.)

Investigational products

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

Test 2

Prednisolone

SUB10018MIG · Substance

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg milligram(s)
Max total dose
945 mg milligram(s)
Max treatment duration
8 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone

SUB10018MIG · Substance

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20
Max total dose
940
Max treatment duration
8 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Placebo tablet (per tablet) Base granulate(3), In-house, Biding/filling agent 152 mg Talc 0 H2O (heated) (4), Ph. Eur. /In-house, Glidant, 6.4 mg Magnesium stearate, Ph. Eur., Lubricant, 1.6 mg 3 Base granulate is an in-house granulate made for tablets with the following composition (5 kg): 4 kg of Lactose (100 M) 1 H2O, 1 kg of Potato starch 0 H2O and approximately 720 ml gelatine spirit. 4 Talc is heated for 30 minutes at 250°C, to destroy spores of clostridium tetani. After heating talc is not additionally analysed.

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leiden University Medical Center

12 Total trials 5 Recruiting 7 Ended
Academic / Non-commercial
Sponsor organisation
Leiden University Medical Center
Address
Albinusdreef 2
City
Leiden
Postcode
2333 ZA
Country
Netherlands

Scientific contact point

Organisation
Leiden University Medical Center
Contact name
Department of gynecology and obstetrics

Public contact point

Organisation
Leiden University Medical Center
Contact name
Department of gynecology and obstetrics

Locations

1 EU/EEA country · 12 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 490 12
Rest of world — 0 —

Investigational sites

Netherlands

12 sites · Ongoing, recruiting
Stichting Radboud University Medical Center
Gynecology and obstetrics, Geert Grooteplein Noord 9, 6525 EZ, Nijmegen
University Hospital Maastricht
Gynecology and Obstetrics, P Debyelaan 25, 6229 HX, Maastricht
Jeroen Bosch Ziekenhuis
Gynecology and obstetrics, Henri Dunantstraat 1, 5223 GZ, 's-Hertogenbosch
Amsterdam UMC
Gynecology and obstetrics, De Boelelaan 1117, 1081 HV, Amsterdam
Catharina Ziekenhuis Stichting
Gynecology and obstetrics, Michelangelolaan 2, 5623 EJ, Eindhoven
Isala Klinieken Stichting
Gynecology and obstetrics, Dokter Van Heesweg 2, 8025 AB, Zwolle
OLVG Stichting
Gynecology and obstetrics, Oosterpark 9, 1091 AC, Amsterdam
Amphia Hospital
Gynecology and obstetrics, Molengracht 21, 4818 CK, Breda
Academisch Ziekenhuis Leiden
Gynecology and obstetrics, Albinusdreef 2, 2333 ZA, Leiden
Universitair Medisch Centrum Groningen
Gynecology and obstetrics, Hanzeplein 1, 9713 GZ, Groningen
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Gynecology and obstetrics, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Medical Center Haaglanden
Gynecology and obstetrics, Lijnbaan 32, 2512 VA, 's-Gravenhage

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 2024-02-13 2024-02-13

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2023-503220-76-00 for publication 1
Protocol (for publication) D1_Protocol 20235032207601 for publication 3
Recruitment arrangements (for publication) K1_ Recruitement arrangements EU CT number 2023-503220-76-00 for publication 1
Recruitment arrangements (for publication) K2_ Recruitement arrangements poster for participants 1
Recruitment arrangements (for publication) K2_ Recruitement arrangements text website Freya NL 1
Recruitment arrangements (for publication) K2_ Recruitment material script animation video for publication 1
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL for publication deelnemend centrum CLEAN 6
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL for publication EMC CLEAN 6
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL for publication LUMC CLEAN 6
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL not for publication deelnemend centrum CLEAN 6
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL not for publication EMC CLEAN 6
Subject information and informed consent form (for publication) L1_ SIS and ICF PREMI NL not for publication LUMC_TC 2
Summary of Product Characteristics (SmPC) (for publication) E1_ IB Prednisolon 1
Synopsis of the protocol (for publication) D1_ Protocol synopsis_ENG EU CT number 2023-503220-76-00 1
Synopsis of the protocol (for publication) D1_ Protocol synopsis_NL EU CT number 2023-503220-76-00 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-07-10 Netherlands Acceptable with conditions
2023-10-02
 2023-10-05
2 SUBSTANTIAL MODIFICATION SM-1 2023-11-30 Netherlands Acceptable
2024-01-29
 2024-01-29
3 SUBSTANTIAL MODIFICATION SM-2 2024-08-28 Netherlands Acceptable
2024-11-05
 2024-11-05