Protamine sulfate has been evaluated in numerous clinical trials encompassing Phase 2 through Phase 4 evaluations as well as early Phase 1 studies. These clinical investigations address diverse medical conditions, ranging from coagulation management and heparin reversal during cardiac surgery to glycemic regulation in patients with type 1 and type 2 diabetes mellitus. Research efforts are supported by diverse sponsors, including academic institutions such as Assistance Publique - Hôpitaux de Paris and pharmaceutical companies like Sanofi and Eli Lilly and Company. Key trials, including NCT06215378 and NCT00965549, span recruitment statuses such as completed, recruiting, and unknown.
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT06215378 | RECRUITING | Aortic Valve Stenosis; Heart Valve Diseases |
Assistance Publique - Hôpitaux de Paris |
2025-05-25 | PHASE3 |
| NCT07477977 | RECRUITING | Open Heart Surgery |
Sohag University |
2026-03-01 | |
| NCT06619301 | RECRUITING | Diabetes Mellitus in Pregnancy; Type 2 Diabetes Mellitus (T2DM); Gestational Diabetes Mellitus, Class A2 |
Loyola University |
2024-04-01 | PHASE3 |
| NCT05774691 | COMPLETED | Aortic Valve Stenosis |
St. Antonius Hospital |
2023-11-01 | PHASE4 |
| NCT05124457 | RECRUITING | Gestational Diabetes; Diabetes Mellitus, Type 2 |
University of California, Los Angeles |
2022-02-01 | PHASE2 |
| NCT06254404 | UNKNOWN | Protamine Dose; Protamine Adverse Reaction |
University of Liege |
2024-03-15 | |
| NCT06154018 | COMPLETED | Cardiac Surgery; CAD; Valve Heart Disease; Coagulation Disorder |
University of Ioannina |
2023-03-18 | |
| NCT05426031 | COMPLETED | Coagulation; Intravascular |
University of Miami |
2022-06-28 | PHASE4 |
| NCT04215588 | COMPLETED | Cardiopulmonary Bypass |
Aristotle University Of Thessaloniki |
2019-12-20 | |
| NCT04628884 | UNKNOWN | Anticoagulant Antagonist Toxicity |
Fundación Clínica Shaio |
2020-11-15 | PHASE4 |
| NCT05709938 | COMPLETED | To Assess the Glycemic Control of Insulin Glargine in Combination With Regular Insulin in Type 1 Diabetes in Children |
King Edward Medical University |
2019-11-01 | PHASE4 |
| NCT03620890 | COMPLETED | Diabetes Mellitus, Type 2 |
The University of Texas Health Science Center, Houston |
2018-09-04 | PHASE4 |
| NCT02974660 | COMPLETED | Aortic Valve Stenosis |
Medical University of Warsaw |
2016-12 | PHASE4 |
| NCT04435912 | COMPLETED | Blood Pressure; Heart Rate; Airway Pressure |
University of Jordan |
2019-07-04 | EARLY_PHASE1 |
| NCT03787641 | UNKNOWN | Cardiac Surgery With Cardiopulmonary Bypass |
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's |
2018-09-20 | |
| NCT03389490 | COMPLETED | Diabetes Mellitus, Type 2 |
Elaine Chow |
2018-01-01 | PHASE4 |
| NCT03532594 | COMPLETED | Heart Diseases; Cardiovascular Diseases |
Papworth Hospital NHS Foundation Trust |
2018-04-16 | |
| NCT04726631 | COMPLETED | Diabetes |
Assiut University |
2015-01-01 | |
| NCT03511521 | TERMINATED | Hyperglycemia Steroid-induced; Insulin Resistance, Diabetes |
Northwestern University |
2018-03-27 | PHASE4 |
| NCT03583567 | COMPLETED | Protamine Adverse Reaction |
Mahidol University |
2018-09-05 | PHASE4 |
| NCT03140631 | COMPLETED | Atrial Fibrillation; Catheter Ablation |
University of Michigan |
2017-03-23 | PHASE4 |
| NCT02189395 | TERMINATED | Type 2 Diabetes Mellitus |
Riverside University Health System Medical Center |
2013-04 | PHASE4 |
| NCT02785575 | UNKNOWN | Cardiac Surgery; Bleeding; Transfusion; Protamine Sulfate; Heparin |
Karolinska University Hospital |
2016-04 | PHASE4 |
| NCT02131272 | TERMINATED | Diabetes; Diabetes Mellitus, Type 2 |
Novo Nordisk A/S |
2014-06-11 | PHASE3 |
| NCT01223131 | COMPLETED | Type 1 Diabetes Mellitus |
Sanofi |
2011-02 | PHASE3 |
| NCT00821795 | COMPLETED | Type 2 Diabetes Mellitus |
Dennis G. Karounos, M.D. |
2009-03-11 | PHASE4 |
| NCT01648218 | TERMINATED | Post-Transplant Glucocorticoid Induced Diabetes |
Vancouver General Hospital |
2012-08 | PHASE4 |
| NCT00965549 | COMPLETED | Diabetes Mellitus, Type 2 |
Sanofi |
2009-07 | PHASE4 |
| NCT01147627 | COMPLETED | Diabetes Mellitus, Type 2; Newly Diagnosed |
Sun Yat-sen University |
2010-08 | |
| NCT01212913 | COMPLETED | Diabetes Mellitus, Type 2 |
Sanofi |
2010-08 | PHASE4 |
| NCT00626080 | COMPLETED | Type 1 Diabetes |
Amsterdam UMC, location VUmc |
2009-01 | |
| NCT00684450 | COMPLETED | Bleeding |
Montreal Heart Institute |
2008-06 | |
| NCT00993473 | COMPLETED | Type 1 Diabetes Mellitus |
Sanofi |
2009-10 | PHASE3 |
| NCT01267487 | COMPLETED | Cardiac Surgery; Cardiopulmonary Bypass; Anticoagulation |
SANE-Society of Anesthesiology |
2009-07 | PHASE4 |
| NCT00666718 | COMPLETED | Diabetes Mellitus, Type 2 |
Eli Lilly and Company |
2008-04 | PHASE3 |
| NCT00560417 | COMPLETED | Diabetes Mellitus, Type 2 |
Eli Lilly and Company |
2007-11 | PHASE3 |
| NCT00510952 | COMPLETED | Diabetes Mellitus, Type 2 |
Eli Lilly and Company |
2007-08 | PHASE3 |
| NCT00494013 | COMPLETED | Diabetes Mellitus Type 2 |
Eli Lilly and Company |
2007-08 | PHASE3 |
| NCT00487240 | COMPLETED | Diabetes Mellitus, Type 1 |
Eli Lilly and Company |
2007-06 | PHASE3 |
| NCT00309244 | COMPLETED | Diabetes Type 2 |
Mannkind Corporation |
2006-02 | PHASE3 |
| NCT00490854 | COMPLETED | Diabetes Mellitus, Type 2 |
Eli Lilly and Company |
2007-07 | PHASE2; PHASE3 |
| NCT00641407 | COMPLETED | Type 2 Diabetes Mellitus; Hypoglycemia |
University of Campania Luigi Vanvitelli |
2007-01 | PHASE4 |
| NCT00073593 | COMPLETED | Cardiac Surgery; Coronary Artery Bypass Surgery |
The Medicines Company |
2003-08 | PHASE3 |
| NCT01336751 | COMPLETED | Diabetes Mellitus, Type 2 |
Sanofi |
2001-07 | PHASE3 |
| NCT00079586 | COMPLETED | Cardiovascular Disease; Coronary Artery Bypass Surgery |
The Medicines Company |
2004-04 | PHASE3 |
| NCT01310452 | UNKNOWN | Type 2 Diabetes Mellitus |
Fudan University |
2011-01 | |
| NCT00191178 | COMPLETED | Type 2 Diabetes |
Eli Lilly and Company |
2003-08 | PHASE4 |
(data from https://clinicaltrials.gov, updated on 2025-08-22)
Check the
Protamine sulfate
product page for in-depth specifications, including solubility, stock solutions, MOA, and working concentrations.
Mechanism and Biochemical Profile
Appendix RUO and cGMP Quality Standards
| Quality Dimension | RUO (Research Use Only) | cGMP (Current Good Manufacturing Practice) |
|---|---|---|
| Clinical Applicability | Prohibited in human clinical trials or medical diagnostics. | Mandatory for human clinical trials (Phase I–III) and therapies. |
| Regulatory Status | Non-regulated grade; exempt from drug manufacturing laws. | Legally enforced by health authorities (e.g., FDA, EMA, NMPA). |
| Facility Environment | Unclassified analytical or research laboratories. | Validated Cleanrooms (ISO Class 5–8) with continuous monitoring. |
| Quality Control | Basic purity and activity testing. | Rigorous safety release testing (Sterility, Endotoxin, Mycoplasma). |
| Process Validation | Basic equipment calibration; no process validation required. | Full qualification (IQ/OQ/PQ) and complete batch records. |
| Quality Assurance | Vendor self-declared without required formal QMS. | Mandatory QA/QC unit, Change Control, CAPA, and vendor audits. |
| Regulatory Impact | High risk of IND rejection if used as a critical raw material. | Required for IND/NDA filings, supported by Drug Master Files (DMF). |
Footnotes
Regulatory Note: Governed by FDA (21 CFR Parts 210/211/312), EMA (EudraLex Vol 4), ICH Guidelines (E6/Q7/Q9/Q10), and compendial standards (USP <71>/<85>/<1043>).
Note: Technical data last updated: Sep 1, 2026.