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PreeclampsiaPhase 3NCT04182373

KW-3357 Study in Patients With Early Onset Severe Preeclampsia

A Phase 3 study testing Antithrombin gamma and physiological saline in people with Preeclampsia, run by Kyowa Kirin Co., Ltd. at 63 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy of intravenous KW-3357 in patients with early-onset severe preeclampsia by comparing the prolongation days of pregnancy with that of placebo. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Preeclampsia
What is being tested?
Antithrombin gamma and physiological saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
181 participants
Where
63 sitesJapan
Study dates
19 Nov 2019to 16 Jun 2023
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who gave written consent to participate in the clinical trial by their own free will.
  • Patients aged 18 years or older at the time of obtaining informed consent
  • Patients with early-onset PE* 24 weeks 0 days to 31 weeks 6 days of gestation at the time of enrollment
  • : Determine the definition of gestational age based on the ""Guidelines for Obstetrics and Gynecology, Obstetrics, 2020""
  • Patients diagnosed with severe PE*
  • : Follow the diagnostic criteria of the Japan Society for the Study of Hypertension in Pregnancy
  • Patients with AT activity of 100% or less in the preliminary examination

Who cannot join

  • Patients who are judged to require immediate delivery*
  • ""Best Practice Guide 2015 for Care and Treatment of Hypertension in Pregnancy"" Requirements for Considering Pregnancy Termination Regardless of Pregnancy Weeks in Pregnancy-induced Hypertension Syndrome Cases will be consulted for judgment.
  • Patients with right hypochondralgia or epigastralgia
  • Patients with HELLP syndromes
  • Patients with pulmonary edema
  • Patients with severe pleural effusion, severe ascites, or serous retinal detachment
Show all 38Show fewer
  • Patients with central nervous system disorders (eclampsia, stroke) or visual disorders (cortical blindness)
  • Patients with severe headache or urge eclampsia
  • Patients with abruptio placentae
  • Suspected patients with 8 or more obstetric DIC scores
  • Patients with a definitive diagnosis of congenital AT deficiency
  • Patients with diseases or symptoms other than the primary disease requiring immediate delivery
  • Patients on ongoing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin) or who require NSAIDs use during the course of the study.
  • Patients who have received the following drugs within 72 hours before administration of the investigational product, etc., or who require administration of the following drugs during the study period (from the start of administration of the investigational product, etc., until the date of termination of pregnancy); heparin, low-molecular-weight heparin (e.g., enoxaparin ordalteparin), fondaparinux, antiplatelet drugs (e.g., clopidogrel, prasugrel, aspirin), direct thrombin inhibitors (e.g., dabigatran), or anticoagulants (e.g., AT preparations).
  • Patients with a current or past history of serious drug allergy
  • Patients with a history or complication of drug dependence or alcoholism
  • Patients with hypersensitivity to AT preparations
  • Patients who are pregnant with a fetus with a chromosomal abnormality or a fetus suspected of having a serious malformation syndrome
  • Patients with multiple pregnancies
  • Patients with a history or complication of antiphospholipid antibody syndrome
  • Patients with diabetes complicated pregnancy or obvious diabetes mellitus
  • Patients with uncontrollable or significant complications, including the following
  • Clinically significant cardiovascular diseases, etc. (New York Heart Association cardiac function classifications Class III or higher)
  • Serious hepatic disease
  • Serious renal disease
  • Pneumonia, interstitial lung disease or other severe respiratory disease
  • Blood disorders such as idiopathic thrombocytopenic purpura
  • Psycho-central nervous system disorders that may affect informed consent
  • Endocrine disorders such as hyperthyroidism
  • Autoimmune diseases such as systemic lupus erythematosus
  • Patients with active malignancy or patients with a history of onset or treatment of malignancy within 5 years before pregnancy (excluding excised or surgically cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or ductal carcinoma of the breast, and excluding cervical intraepithelial neoplasia regardless of excised or surgically cured or not)
  • Patients with active infections (e.g., toxoplasma infection, genital chlamydia, genital herpes, cytomegalovirus infection)
  • Patients with a positive history for HIV antibody. Patients with a positive history for HBs antigen and HCV antibody and with active infection presenting with hepatitis symptoms.
  • Patients with any of the following laboratory abnormalities in preliminary examinations
  • Patients with AST or ALT 2 times the upper limit of the reference level of the trial site
  • Cr >=1.1 mg/dL
  • Patients who have participated in a clinical trial or equivalent study of a drug or medical device within 4 months before pregnancy (within 6 months for biologics) and have received the investigational drug or used an unapproved medical device
  • Other patients whom the principal investigator or the subinvestigator judges to be unfavorable for participation in the clinical trial

Trial locations and contacts

63 sites in 1 country.

63 sites in 1 country

Japan63 sites

  • Osaka Metropolitan University Hospital

    Abeno-ku, Osaka

  • Aomori Prefectural Central Hospital

    Aomori

  • The University of Tokyo Hospital

    Bunkyo, Tokyo

  • Juntendo University Hospital

    Bunkyo-ku, Tokyo

  • Tokyo Metropolitan Tama Medical Center

    Fuchū, Tokyo

  • Fukuoka University Hospital

    Fukuoka

  • Hakodate Central General Hospital

    Hakodate, Hokkaido

  • Hamamatsu Medical Center

    Hamamatsu, Shizuoka

  • Hamamatsu University Hospital

    Hamamatsu, Shizuoka

  • Japanese Red Cross Society Himeji Hospital

    Himeji, Hyōgo

  • Kansai Medical University Hospital

    Hirakata, Osaka

  • Iwate Medical University Hospital

    Hizume, Iwate

  • Osaka Women's and Children's Hospital

    Izumi, Osaka

  • Rinku General Medical Center

    Izumisano, Osaka

  • Juntendo University Shizuoka Hospital

    Izunokuni, Shizuoka

  • Kagoshima City Hospital

    Kagoshima

  • Ishikawa Prefectural Central Hospital

    Kanazawa, Ishikawa-ken

  • Nara Medical University Hospital

    Kashihara, Nara

  • Saitama Medical Center

    Kawagoe, Saitama

  • St. Marianna University School of Medicine

    Kawasaki, Kanagawa

  • National Hospital Organization Kokura Medical Center

    Kitakyushu, Fukuoka

  • Kobe University Hospital

    Kobe, Hyōgo

  • Yamanashi Prefectural Central Hospital

    Kofu, Yamanashi

  • Kumamoto University Hospital

    Kumamoto

  • Kurume University Hospital

    Kurume, Fukuoka

  • Our Lady of the Snow Social Medical Corporation St. Mary's Hospital

    Kurume, Fukuoka

  • Kyoto University Hospital

    Kyoto

  • University Hospital Kyoto Prefectural University of Medicine

    Kyoto

  • Shinshu University Hospital

    Matsumoto, Nagano

  • Dokkyo Medical University Hospital

    Mibu, Tochigi

  • Aiiku Hospital

    Minato, Tokyo

  • Kyorin University Hospital

    Mitaka, Tokyo

  • Faculty of Medicine, University of Miyazaki Hospital

    Miyazaki

  • Nagasaki University Hospital

    Nagasaki

  • Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

    Nagoya, Aichi-ken

  • Nara Prefecture General Medical Center

    Nara

  • Niigata University Medical & Dental Hospital

    Niigata

  • Obihiro Kosei General Hospital

    Obihiro, Hokkaido

  • Oita Prefectural Hospital

    Ōita

  • Okayama University Hospital

    Okayama

  • National Hospital Organization Nagasaki Medical Center

    Ōmura, Nagasaki

  • Osaka City General Hospital

    Osaka

  • The Kitasato Institute Kitasato University Hospital

    Sagamihara, Kanagawa

  • Hokkaido University Hospital

    Sapporo, Hokkaido

  • Sapporo City General Hospital

    Sapporo, Hokkaido

  • Sendai Red Cross Hospital

    Sendai, Miyagi

  • National Center for Child Health and Development

    Setagaya City, Tokyo

  • Japanese Red Cross Medical Center

    Shibuya City, Tokyo

  • Jichi Medical University Hospital

    Shimotsuke, Tochigi

  • Showa University Hospital

    Shinagawa, Tokyo

  • National Cerebral and Cardiovascular Center

    Suita, Osaka

  • Tokyo Metropolitan Bokutoh Hospital

    Sumida City, Tokyo

  • Ehime University Hospital

    Tōon, Ehime

  • Toyama University Hospital

    Toyama

  • Fujita Health University Hospital

    Toyoake, Aichi-ken

  • Toyota Memorial Hospital

    Toyota, Aichi-ken

  • Mie University Hospital

    Tsu, Mie-ken

  • Yamaguchi University Hospital

    Ube, Yamaguchi

  • Juntendo University Urayasu Hospital

    Urayasu, Chiba

  • Okinawa prefectural Chubu Hospital

    Uruma, Okinawa

  • Tokyo Women's Medical University Yachiyo Medical Center

    Yachiyo, Chiba

  • Yokohama City University Medical Center

    Yokohama, Kanagawa

  • National Hospital Organization Shikoku Medical Center for Children and Adults

    Zentsujichó, Kagawa-ken

Other trials in Japan

About this study

Official title: A Phase 3, Randomized, Placebo-controlled, Double Blind Study of KW-3357 in Patients With Early Onset Severe Preeclampsia

The purpose of this study is to evaluate the efficacy of intravenous KW-3357 in patients with early-onset severe preeclampsia by comparing the prolongation days of pregnancy with that of placebo.

Conditions
Preeclampsia
Being tested
Antithrombin gamma, physiological saline
Keywords
Preeclampsia, Antithrombin
Medical subject headings
Pre-Eclampsia

What participants receive

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

  • Antithrombin gammaDrug

    Intravenous infusion, once a day, 7 days

  • physiological salineDrug

    Intravenous infusion, once a day, 7 days

Study groups in NCT04182373
Study groupRoleWhat they receive
KW-3357Experimental72 IU/kg
Receives: Drug: Antithrombin gamma
placeboPlacebo comparatorNot described
Receives: Drug: physiological saline

What is being measured

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

  1. Days of maintaining pregnancy

    Measured: Subjects will be observed until maternal and/or fetal indications for delivery necessitate cessation of expectant management or until approximately 34 0/7 weeks of gestation.

Secondary outcomes (22)

  1. Presence or absence of achievement of 32 weeks of gestation

    Measured: 28 days before the end of study

  2. Presence or absence of achievement of 34 weeks of gestation

    Measured: 28 days before the end of study

  3. Presence or absence of achievement of 28 weeks of gestation in subjects enrolled in the period of less than 28 weeks of gestation

    Measured: 28 days before the end of study

  4. Change in AT activity

    Measured: From baseline to Day 8 at all time points and 3 days after termination of pregnancy

  5. Change in PLT concentration

    Measured: From baseline to Day 8 at all time points and 3 days after termination of pregnancy

  6. Change on D-dimer concentration

    Measured: From baseline to Day 8 at all time points

  7. Change in FDP concentration

    Measured: From baseline to Day 8 at all time points

  8. Sitting systolic blood pressure and sitting diastolic blood pressure

    Measured: From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy

  9. Proteinuria/creatinine ratio

    Measured: From baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy

  10. Amount of blood lost during delivery

    Measured: 28 days before the end of study

  11. Biophysical Profile Score

    Minimum is 0, max is 10. Higher score means better condition.

    Measured: From baseline to Day 8 at each time point

  12. Fetal growth rate

    Measured: 28 days before the end of study

  13. Apgar score

    Minimum is 0, max is 10. Higher score means better condition.

    Measured: At 1 minute and 5 minutes after birth

  14. Presence or absence of neonatal asphyxia

    Measured: At 1 minute and 5 minutes after birth

  15. Birth weight

    Measured: 28 days before the end of study

  16. Neonatal growth

    Fetal growth is classified into small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA).

    Measured: 28 days before the end of study

  17. Head and chest circumferences at birth

    Measured: 28 days before the end of study

  18. Short-term prognosis of neonates (incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukolame, retinopathy of prematurity, sepsis, necrotizing enteritis, death, etc)

    Measured: 28 days after termination of pregnancy

  19. The number of neonates who was hospitalized in the NICU

    Measured: 28 days after termination of pregnancy

  20. The number of days in the NICU

    Measured: 28 days after termination of pregnancy

  21. The number of neonates with respiratory management at the time of admission to the NICU

    Measured: 28 days after termination of pregnancy

  22. The number of days of respiratory management at the time of admission to the NICU

    Measured: 28 days after termination of pregnancy

Timeline

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

  1. First posted2 Dec 2019
  2. Study start19 Nov 2019
  3. Primary completion17 May 2023
  4. Study completion16 Jun 2023

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
181 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04182373
Sponsor's protocol ID
3357-101
Status last verified
Nov 2023
First submitted
10 Oct 2019
Last updated
15 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin will be available in the Vivli repository, https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Publications

  • Saito S, Takagi K, Moriya J, Kobayashi T, Kanayama N, Sameshima H, Morikawa M, Sago H, Adachi T, Ohkuchi A, Takeda S, Masuyama H, Seki H. A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol. Contemp Clin Trials. 2021 Aug;107:106490. doi: 10.1016/j.cct.2021.106490. Epub 2021 Jun 24.

    PubMed 34174463

  • Takeda J, Tachibana D, Itakura A, Takagi K, Nakami S, Mano H, Kobayashi T, Kanayama N, Sameshima H, Morikawa M, Sago H, Adachi T, Ohkuchi A, Takeda S, Masuyama H, Seki H, Saito S; KOUNO-TORI Study Group. Randomized Study of Antithrombin in Early-Onset Preeclampsia: KOUNO-TORI Study. Hypertension. 2026 Jun;83(6):e25431. doi: 10.1161/HYPERTENSIONAHA.125.25431. Epub 2026 Mar 6.

    PubMed 41789451

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Antithrombin gamma and physiological saline in people with Preeclampsia, run by Kyowa Kirin Co., Ltd. at 63 sites in Japan.

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 38 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: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 63 sites in Japan. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Days of maintaining pregnancy (time frame: Subjects will be observed until maternal and/or fetal indications for delivery necessitate cessation of expectant management or until approximately 34 0/7 weeks of gestation.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04182373, which also lists 2 linked publications.

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 15 Nov 2023.

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