NCT03461835

Brief Summary

In a randomized multicenter trial the investigators want to compare the ability of two hCG-based models in correctly classifying EPs as high risk among PULs and correctly classifying IUPs and failed PULs as low risk after two hCG measurements. After the classification of PULs into high or low risk of EP, the clinical management will be the same within each risk group (high and low) regardless of randomization group (which model classified the patients). The clinical management will be according to the management protocol published in a NICE guideline.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
609

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Feb 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2018

Completed
13 days until next milestone

Study Start

First participant enrolled

February 22, 2018

Completed
18 days until next milestone

First Posted

Study publicly available on registry

March 12, 2018

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2024

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2024

Completed
Last Updated

April 6, 2025

Status Verified

April 1, 2025

Enrollment Period

6.5 years

First QC Date

February 9, 2018

Last Update Submit

April 3, 2025

Conditions

Pregnancy, EctopicPregnancy, High RiskPregnancy Early

Outcome Measures

Primary Outcomes (2)

  • Sensitivity

    EPs (percent) correctly classified as high risk of being an EP among PULs

    1 month

  • Specificity

    IUPs and failed PULs (percent) correctly classified as low risk of being an EP among PULs

    1 month

Secondary Outcomes (10)

  • HAD (Hospital and anxiety scale)

    1 month

  • Follow up visits (efficacy)

    1 month

  • Adverse events

    1 month

  • Deviation from PUL management protocol

    1 month

  • Treatment of ectopic pregnancy

    1 month

  • +5 more secondary outcomes

Study Arms (2)

M4

ACTIVE COMPARATOR

High risk classification if the chance of the PUL being an EP ≥5 %; a calculation based on the average value of the two hCG and the ratio of these two hCG (0 h/48 h). Otherwise a low risk classification is made and a predicted outcome of either an IUP or failed PUL is presented.

Diagnostic Test: Risk classification of PUL by M4Diagnostic Test: Risk classification of PUL by NICE

NICE

ACTIVE COMPARATOR

High risk classification if the change in rising hCG levels ≤ 63 % or the change in declining hCG ≤ 50 %. If these cut-offs are exceeded the PUL is classified as low risk and predicted to be either an IUP or failed PUL depending on rising or declining hCG levels.

Diagnostic Test: Risk classification of PUL by M4Diagnostic Test: Risk classification of PUL by NICE

Interventions

Risk classification of PUL by M4DIAGNOSTIC_TEST

High or low risk of being an ectopic pregnancy

M4NICE
Risk classification of PUL by NICEDIAGNOSTIC_TEST

High or low risk of being an ectopic pregnancy

M4NICE

Eligibility Criteria

Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with a PUL
  • Patients with mild or no symptoms
  • Patients willing to be randomized
  • First hCG value \<10,000 IU/L
  • Patients with an interval between two hCG measurements of 44-56 h

You may not qualify if:

  • Hemodynamically unstable patients
  • Hemoperitoneum
  • Patients not managed as outpatients during the course of the initial two hCG measurements
  • Non-understanding of the oral or written study information

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Södra Älvsborgs Sjukhus

Borås, 501 82, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Skaraborgs sjukhus Skövde

Skövde, 541 85, Sweden

Location

Related Publications (8)

  • Barnhart K, van Mello NM, Bourne T, Kirk E, Van Calster B, Bottomley C, Chung K, Condous G, Goldstein S, Hajenius PJ, Mol BW, Molinaro T, O'Flynn O'Brien KL, Husicka R, Sammel M, Timmerman D. Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertil Steril. 2011 Mar 1;95(3):857-66. doi: 10.1016/j.fertnstert.2010.09.006. Epub 2010 Oct 14.

    PMID: 20947073BACKGROUND

  • van Mello NM, Mol F, Opmeer BC, Ankum WM, Barnhart K, Coomarasamy A, Mol BW, van der Veen F, Hajenius PJ. Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov-Dec;18(6):603-17. doi: 10.1093/humupd/dms035. Epub 2012 Sep 6.

    PMID: 22956411BACKGROUND

  • National Collaborating Centre for Women's and Children's Health (UK). Ectopic Pregnancy and Miscarriage: Diagnosis and Initial Management in Early Pregnancy of Ectopic Pregnancy and Miscarriage. London: RCOG Press; 2012 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK132775/

    PMID: 23638497BACKGROUND

  • Van Calster B, Abdallah Y, Guha S, Kirk E, Van Hoorde K, Condous G, Preisler J, Hoo W, Stalder C, Bottomley C, Timmerman D, Bourne T. Rationalizing the management of pregnancies of unknown location: temporal and external validation of a risk prediction model on 1962 pregnancies. Hum Reprod. 2013 Mar;28(3):609-16. doi: 10.1093/humrep/des440. Epub 2013 Jan 4.

    PMID: 23293216BACKGROUND

  • Fistouris J, Bergh C, Strandell A. Classification of pregnancies of unknown location according to four different hCG-based protocols. Hum Reprod. 2016 Oct;31(10):2203-11. doi: 10.1093/humrep/dew202. Epub 2016 Aug 31.

    PMID: 27580995BACKGROUND

  • Mavrelos D, Nicks H, Jamil A, Hoo W, Jauniaux E, Jurkovic D. Efficacy and safety of a clinical protocol for expectant management of selected women diagnosed with a tubal ectopic pregnancy. Ultrasound Obstet Gynecol. 2013 Jul;42(1):102-7. doi: 10.1002/uog.12401. Epub 2013 May 27.

    PMID: 23303651BACKGROUND

  • Bobdiwala S, Guha S, Van Calster B, Ayim F, Mitchell-Jones N, Al-Memar M, Mitchell H, Stalder C, Bottomley C, Kothari A, Timmerman D, Bourne T. The clinical performance of the M4 decision support model to triage women with a pregnancy of unknown location as at low or high risk of complications. Hum Reprod. 2016 Jul;31(7):1425-35. doi: 10.1093/humrep/dew105. Epub 2016 May 10.

    PMID: 27165655BACKGROUND

  • Fistouris J, Garbergs H, Bergman K, Bergh C, Strandell A. Managing Pregnancies of Unknown Location With the M4 Prediction Model or the NICE Algorithm: A Randomised Controlled Trial With Cross-Sectional Diagnostic Accuracy Data. BJOG. 2025 May;132(6):742-751. doi: 10.1111/1471-0528.18079. Epub 2025 Jan 22.

    PMID: 39840550DERIVED

MeSH Terms

Conditions

Pregnancy, Ectopic

Condition Hierarchy (Ancestors)

Pregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Study Officials

  • Annika Strandell, Ass.prof.

    Göteborg University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 9, 2018

First Posted

March 12, 2018

Study Start

February 22, 2018

Primary Completion

August 30, 2024

Study Completion

December 30, 2024

Last Updated

April 6, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

SE(3)