Study to Use Oral Losartan to Decrease the Risk of Postoperative Scarring Following (ACL) Reconstruction

Rush

Status and phase

Begins enrollment in 5 months

Phase 4

Conditions

Scar Formation

ACL Injury

ACL Reconstruction

Treatments

Other: Placebo

Drug: Losartan

Study type

Interventional

Funder types

Other

Identifiers

NCT07135687

24120601

Details and patient eligibility

About

The purpose of this study to investigate the effect of using losartan (a blood pressure lowering drug with anti-scarring properties) on preventing primary postoperative arthrofibrosis (formation of abnormal scar tissue) in the knees in participants undergoing anterior cruciate ligament (ACL) repair surgery of their knee.

Full description

Losartan, an angiotensin-II receptor blocker (ARB), approved by the Food and Drug Administration (FDA) for the treatment of hypertension and diabetic nephropathy, has garnered recent interest in the field of orthopedic surgery as an anti-fibrotic (anti-scarring) agent. Losartan's primary mechanism of action as an anti-hypertensive involves acting as a receptor antagonist for angiotensin II, a peptide produced by the liver which causes vasoconstriction, release of anti-diuretic hormone from the pituitary gland, and release of aldosterone from the adrenal glands, among other functions. Losartan secondary function is to act as a TGF-β1 blocker. TGF-β1 has been implicated in pro-fibrotic pathways in multiple organs systems. Losartan, initially as a treatment for hypertension and diabetic nephropathy, was found to have benefits against fibrosis in the renal system. As a result, the use of losartan has gained interest in several other fields in medicine, including plastic surgery for wound healing and keloid prevention, in ophthalmology to prevent corneal scarring, and orthopedic surgery. The potential use of losartan presents an attractive anti-fibrotic prophylaxis candidate against the formation of postoperative arthrofibrosis following ACLR.

Enrollment

144 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Must be undergoing a primary ACLR with or without the following:
Chondroplasty
Synovectomy
Loose body removal
Removal of hardware
Meniscal surgery (excluding meniscal allograft transplantation/MAT)
Lateral extra-articular tenodesis
Must have skeletal maturity in the distal femur and proximal tibial physes
Must be age 18 years or older at time of enrollment

Exclusion criteria

<18 years at time of enrollment
No diagnosis of ACL tear
ACL repairs
Revision ACL reconstructions
Open distal femur or proximal tibia physes
Major concomitant procedures (such as osteotomy, MAT, or cartilage restoration surgery)
History of prior proximal or distal femur fracture (including those receiving nonoperative treatment)
History of prior ipsilateral femur or tibia osteomyelitis
Medical history
History of hypotensive disease, including postural orthostatic hypotension syndrome (POTS), autonomic dysreflexia, or Shy-Drager syndrome (aka multiple system atrophy), baseline hypotension <90 systolic or <60 diastolic mmHg.
History of significant hepatic disease (liver transplantation, cirrhosis of any cause, or any liver disease with Child-Pugh classification B or C) due to hepatic metabolism of ARBs.
Chronic kidney disease
Rheumatologic disorders on immunologic medications
Current medications including diuretics (i.e. furosemide), lithium, and spironolactone
Current hypertension with prescription of an ARB or ACE-I
Allergy to losartan
Current pregnancy or breastfeeding