Progesterone in the Treatment of Acute Hemorrhagic Stroke

An International Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial of Progesterone Combined Intranasal and Intramuscular Administration in Patients With Acute Hemorrhagic Stroke

A large number of preclinical studies have confirmed that progesterone and its metabolites have strong neuroprotective effects. As a neuroprotective agent, progesterone has been effective in several animal models of nerve injury, suggesting that the drug has a wide range of neuroprotective effects. Pharmacodynamic studies have shown that some characteristic mechanisms of the action of the neurosteroid on brain injury and cerebral congestion include: prevention of inflammatory reaction and cell death (by inhibiting the activation of inflammatory cytokines and microglia); control of angiogenic brain edema (by reestablishing blood-brain barrier and regulating aquaporin-4 water transporter) and cytotoxic edema (by regulating Progesterone can also improve the neural dysfunction after cerebral hemorrhage, promote the regeneration and repair of damaged axons (activate PI3K / Akt pathway to inhibit the expression of RhoA), prevent the loss of Ca2 + caused by excitotoxicity and improve the survival rate of neurons. It was found that progesterone injection could reduce brain edema and promote the recovery of nerve function after brain injury.

Study Overview

• Status: Unknown
• Conditions: Stroke
• Intervention / Treatment: Drug: Progesterone; Other: saline

Detailed Description

The purpose of this clinical trial is to further evaluate the safety and effectiveness of progesterone in the clinical application of major cerebral congestion diseases. The Second Affiliated Hospital of Zhejiang University is the unit in charge of clinical research, and six units participate in the multicenter randomized, double-blind, placebo-controlled clinical trial.

• Study Type: Interventional
• Enrollment (Anticipated): 184
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute hemorrhagic stroke was confirmed by CT or MRI. There should be no obvious sequelae symptoms in the first stroke or previous stroke, Mrs < 2 (slight or no neurological dysfunction).
• Patients aged 40-80 (male, menopausal women);
• Patients with 6-48 hours of onset;
• 3 points ≤ NIHSS score ≤ 15 points for light and medium patients;
• Patients or family members sign informed consent.

Exclusion Criteria:

• Cerebral CT has excluded intracranial hemorrhage, and there is no imaging change of early large area cerebral infarction.
• Pregnant or lactating women;
• Previous intracranial hemorrhage, including suspected subarachnoid hemorrhage; large area stroke (> 2 / 3 MCA territory) or head CT showed any degree of midline displacement due to brain edema. Signs of intracranial hemorrhage (ICH, SAH, extradural hemorrhage, acute or chronic SDH) were found on baseline CT or MRI scan.
• Fever, defined as central body temperature > 37.5 ℃;
• Patients with severe heart, liver and kidney dysfunction or severe diabetes;
• Platelet count was less than 100 × 109 / L, blood glucose was less than 27 mmol / L, serum creatinine was more than 2.0 mg / dL or 180 μ mol / L.
• Blood pressure: systolic pressure > 180 mmHg, or diastolic pressure > 100 mmHg;
• Those who have previous allergic history to progesterone and citicoline;
• The anticoagulant has been taken orally, and INR is more than 15; heparin has been taken within 48 hours (APTT is beyond the normal range);
• Participating in clinical trials of any other treatment;
• Patients considered by the researchers not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; Progesterone	Drug: Progesterone; intramuscular injection intranasal administration; Other Names: progesterone injection
Placebo Comparator: control grou; saline	Other: saline; intramuscular injection intranasal administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale	The percentage of patients with Mrs score 0, 1 and 2 was compared.	3 month

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Seoul National University Hospital; Korea University Anam Hospital; Jinhua Central Hospital; Huizhou Municipal Central Hospital; Lishui Country People's Hospital; The Affiliated Hospital of Hangzhou Normal University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): October 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: October 27, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Hemorrhagic Stroke; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: YANWQ001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No