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KW-3357 Study in Patients With Early Onset Severe Preeclampsia

Phase 3
Completed
Conditions
Preeclampsia
Interventions
Drug: physiological saline
Registration Number
NCT04182373
Lead Sponsor
Kyowa Kirin Co., Ltd.
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
181
Inclusion Criteria
  1. Patients who gave written consent to participate in the clinical trial by their own free will.

  2. Patients aged 18 years or older at the time of obtaining informed consent

  3. 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""

  4. Patients diagnosed with severe PE*

    *: Follow the diagnostic criteria of the Japan Society for the Study of Hypertension in Pregnancy

  5. Patients with AT activity of 100% or less in the preliminary examination

Exclusion Criteria
  1. 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.

  2. Patients with right hypochondralgia or epigastralgia

  3. Patients with HELLP syndromes

  4. Patients with pulmonary edema

  5. Patients with severe pleural effusion, severe ascites, or serous retinal detachment

  6. Patients with central nervous system disorders (eclampsia, stroke) or visual disorders (cortical blindness)

  7. Patients with severe headache or urge eclampsia

  8. Patients with abruptio placentae

  9. Suspected patients with 8 or more obstetric DIC scores

  10. Patients with a definitive diagnosis of congenital AT deficiency

  11. Patients with diseases or symptoms other than the primary disease requiring immediate delivery

  12. Patients on ongoing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., aspirin) or who require NSAIDs use during the course of the study.

  13. 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).

  14. Patients with a current or past history of serious drug allergy

  15. Patients with a history or complication of drug dependence or alcoholism

  16. Patients with hypersensitivity to AT preparations

  17. Patients who are pregnant with a fetus with a chromosomal abnormality or a fetus suspected of having a serious malformation syndrome

  18. Patients with multiple pregnancies

  19. Patients with a history or complication of antiphospholipid antibody syndrome

  20. Patients with diabetes complicated pregnancy or obvious diabetes mellitus

  21. 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
  22. 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)

  23. Patients with active infections (e.g., toxoplasma infection, genital chlamydia, genital herpes, cytomegalovirus infection)

  24. 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.

  25. 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
  26. 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

  27. Other patients whom the principal investigator or the subinvestigator judges to be unfavorable for participation in the clinical trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placebophysiological saline-
KW-3357Antithrombin gamma72 IU/kg
Primary Outcome Measures
NameTimeMethod
Days of maintaining pregnancySubjects 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 Outcome Measures
NameTimeMethod
Presence or absence of achievement of 34 weeks of gestation28 days before the end of study
Presence or absence of achievement of 28 weeks of gestation in subjects enrolled in the period of less than 28 weeks of gestation28 days before the end of study
Change in AT activityFrom baseline to Day 8 at all time points and 3 days after termination of pregnancy
Change in PLT concentrationFrom baseline to Day 8 at all time points and 3 days after termination of pregnancy
Change on D-dimer concentrationFrom baseline to Day 8 at all time points
Change in FDP concentrationFrom baseline to Day 8 at all time points
Sitting systolic blood pressure and sitting diastolic blood pressureFrom baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
Presence or absence of achievement of 32 weeks of gestation28 days before the end of study
Proteinuria/creatinine ratioFrom baseline to Day 8 at each time point, 3 days after termination of pregnancy, and 28 days after termination of pregnancy
Amount of blood lost during delivery28 days before the end of study
Biophysical Profile ScoreFrom baseline to Day 8 at each time point

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

Fetal growth rate28 days before the end of study
Apgar scoreAt 1 minute and 5 minutes after birth

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

Presence or absence of neonatal asphyxiaAt 1 minute and 5 minutes after birth
Birth weight28 days before the end of study
Neonatal growth28 days before the end of study

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

Head and chest circumferences at birth28 days before the end of study
Short-term prognosis of neonates (incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukolame, retinopathy of prematurity, sepsis, necrotizing enteritis, death, etc)28 days after termination of pregnancy
The number of neonates who was hospitalized in the NICU28 days after termination of pregnancy
The number of days in the NICU28 days after termination of pregnancy
The number of neonates with respiratory management at the time of admission to the NICU28 days after termination of pregnancy
The number of days of respiratory management at the time of admission to the NICU28 days after termination of pregnancy

Trial Locations

Locations (63)

National Center for Child Health and Development

🇯🇵

Setagaya, Tokyo, Japan

Aiiku Hospital

🇯🇵

Minato, Tokyo, Japan

Okinawa prefectural Chubu Hospital

🇯🇵

Uruma, Okinawa, Japan

National Hospital Organization Kokura Medical Center

🇯🇵

Kitakyushu, Fukuoka, Japan

Kurume University Hospital

🇯🇵

Kurume, Fukuoka, Japan

Yamaguchi University Hospital

🇯🇵

Ube, Yamaguchi, Japan

Kagoshima City Hospital

🇯🇵

Kagoshima, Japan

Fujita Health University Hospital

🇯🇵

Toyoake, Aichi, Japan

Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

🇯🇵

Nagoya, Aichi, Japan

Toyota Memorial Hospital

🇯🇵

Toyota, Aichi, Japan

Juntendo University Urayasu Hospital

🇯🇵

Urayasu, Chiba, Japan

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

🇯🇵

Kurume, Fukuoka, Japan

Tokyo Women's Medical University Yachiyo Medical Center

🇯🇵

Yachiyo, Chiba, Japan

Ehime University Hospital

🇯🇵

Toon, Ehime, Japan

Obihiro Kosei General Hospital

🇯🇵

Obihiro, Hokkaido, Japan

Hakodate Central General Hospital

🇯🇵

Hakodate, Hokkaido, Japan

Hokkaido University Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Sapporo City General Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Kobe University Hospital

🇯🇵

Kobe, Hyogo, Japan

Japanese Red Cross Society Himeji Hospital

🇯🇵

Himeji, Hyogo, Japan

Iwate Medical University Hospital

🇯🇵

Shiwa, Iwate, Japan

Ishikawa Prefectural Central Hospital

🇯🇵

Kanazawa, Ishikawa, Japan

National Hospital Organization Shikoku Medical Center for Children and Adults

🇯🇵

Zentsuji, Kagawa, Japan

St. Marianna University School of Medicine

🇯🇵

Kawasaki, Kanagawa, Japan

The Kitasato Institute Kitasato University Hospital

🇯🇵

Sagamihara, Kanagawa, Japan

Yokohama City University Medical Center

🇯🇵

Yokohama, Kanagawa, Japan

Mie University Hospital

🇯🇵

Tsu, Mie, Japan

Sendai Red Cross Hospital

🇯🇵

Sendai, Miyagi, Japan

National Hospital Organization Nagasaki Medical Center

🇯🇵

Omura, Nagasaki, Japan

Shinshu University Hospital

🇯🇵

Matsumoto, Nagano, Japan

Osaka Metropolitan University Hospital

🇯🇵

Abeno-ku, Osaka, Japan

Nara Medical University Hospital

🇯🇵

Kashihara, Nara, Japan

Kansai Medical University Hospital

🇯🇵

Hirakata, Osaka, Japan

Rinku General Medical Center

🇯🇵

Izumisano, Osaka, Japan

Osaka Women's and Children's Hospital

🇯🇵

Izumi, Osaka, Japan

Saitama Medical Center

🇯🇵

Kawagoe, Saitama, Japan

Hamamatsu University Hospital

🇯🇵

Hamamatsu, Shizuoka, Japan

National Cerebral and Cardiovascular Center

🇯🇵

Suita, Osaka, Japan

Hamamatsu Medical Center

🇯🇵

Hamamatsu, Shizuoka, Japan

Juntendo University Hospital

🇯🇵

Bunkyo-ku, Tokyo, Japan

Juntendo University Shizuoka Hospital

🇯🇵

Izunokuni, Shizuoka, Japan

Jichi Medical University Hospital

🇯🇵

Shimotsuke, Tochigi, Japan

Dokkyo Medical University Hospital

🇯🇵

Mibu, Tochigi, Japan

The University of Tokyo Hospital

🇯🇵

Bunkyo, Tokyo, Japan

Tokyo Metropolitan Tama Medical Center

🇯🇵

Fuchu, Tokyo, Japan

Kyorin University Hospital

🇯🇵

Mitaka, Tokyo, Japan

Tokyo Metropolitan Bokutoh Hospital

🇯🇵

Sumida, Tokyo, Japan

Yamanashi Prefectural Central Hospital

🇯🇵

Kofu, Yamanashi, Japan

Aomori Prefectural Central Hospital

🇯🇵

Aomori, Japan

Kyoto University Hospital

🇯🇵

Kyoto, Japan

Kumamoto University Hospital

🇯🇵

Kumamoto, Japan

Fukuoka University Hospital

🇯🇵

Fukuoka, Japan

University Hospital Kyoto Prefectural University of Medicine

🇯🇵

Kyoto, Japan

Faculty of Medicine, University of Miyazaki Hospital

🇯🇵

Miyazaki, Japan

Oita Prefectural Hospital

🇯🇵

Oita, Japan

Niigata University Medical & Dental Hospital

🇯🇵

Niigata, Japan

Nara Prefecture General Medical Center

🇯🇵

Nara, Japan

Okayama University Hospital

🇯🇵

Okayama, Japan

Osaka City General Hospital

🇯🇵

Osaka, Japan

Toyama University Hospital

🇯🇵

Toyama, Japan

Nagasaki University Hospital

🇯🇵

Nagasaki, Japan

Japanese Red Cross Medical Center

🇯🇵

Shibuya, Tokyo, Japan

Showa University Hospital

🇯🇵

Shinagawa, Tokyo, Japan

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