NCT02263729

Phase 1/2 Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial of Losartan to Treat Grade II & III Hamstring Strains

Terminated Phase 1, PHASE2 Results posted Last updated 2 May 2024

What this trial tests

Phase 1, PHASE2 trial testing Losartan in Hamstring Injury in 8 participants. Terminated before completion.

Timeline

10 August 2016

Primary endpoint
31 December 2022

31 December 2022

Quick facts

Lead sponsor	James J. Irrgang
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	8
Start date	10 August 2016
Primary completion	31 December 2022
Estimated completion	31 December 2022
Sites	1 location across United States

Drugs / interventions tested

• Losartan (losartan) — full drug profile →
• Placebo

Conditions studied

• Hamstring Injury — all drugs for Hamstring Injury →

Sponsor

James J. Irrgang

Who can join

18 and older, any sex, with Hamstring Injury. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Reported Effects of Losartan for Hamstring Injury for Safety and Tolerability Primary · 4 weeks

Directly related to specific aim 1- Side effects, safety, and tolerability will be monitored by measuring vital signs, lab values via blood work, and number of adverse events, serious adverse events, and patient reported side effects.

Group	Value	95% CI
Losartan	0
Placebo	0
Losartan	0
Placebo	0
Losartan	0
Placebo	0
Losartan	0
Placebo	0

Recovery of Hamstring Muscle Function Primary · 6 weeks; 6 months

For specific aim 2, hamstring muscle function of the injured leg was measured and compared to the contralateral leg using isometric hamstring force at 30, 60, and 90 degrees of knee flexion at 6 weeks and 6 months. Data are expressed as a Limb Symmetry Index (LSI), which is the percent force of the injured hamstring compared to the force of the non-injured hamstring muscle.

6 weeks: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	91	42 – 139
Placebo	75	21 – 129

6 weeks: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	102	67 – 137
Placebo	77	69 – 85

6 weeks: Limb Symmetry Index isometric strength at 60 deg knee flexion (Biodex)

Group	Value	95% CI
Losartan	79	59 – 98
Placebo	73	15 – 130

6 months: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	107	0 – 323
Placebo	95	0 – 355

6 months: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	106	0 – 290
Placebo	76	0 – 590

6 months: Limb Symmetry Index isometric strength at 60 deg knee flexion (%, Biodex)

Group	Value	95% CI
Losartan	83	45 – 121
Placebo	104

Recovery of Hamstring Structure Primary · 6 months

For specific aim 2, recovery of hamstring structure was measured as the length of injury at 6 months as well as the change in proximal-distal length of injury from baseline to 6 month post-treatment MRI. Greater change in length represents greater healing.

Proximal-distal length of injury measured (MRI)

Group	Value	95% CI
Losartan	0.8
Placebo	5.6	0 – 67

Change in proximal-distal length of injury from baseline (MRI)

Group	Value	95% CI
Losartan	23
Placebo	17.6	0 – 140

Recovery of Hamstring Structure Primary · 6 months

For specific aim 2, hamstring structure was measured in terms of the volume of fibrosis at 6 month MRI, as such smaller volume of fibrosis represents greater healing of the hamstring muscle. Hamstring structure was also determined by comparing the change of pre-treatment volume of the injury on the baseline MRI to the volume of fibrosis on the 6 month MRI.

Volume of fibrosis at 6 months (MRI)

Group	Value	95% CI
Losartan	0.6
Placebo	0.7	0 – 3

Change of pre-treatment volume of the injury to 6 months (MRI)

Group	Value	95% CI
Losartan	138.4
Placebo	1028	0 – 10691

Return to Prior Level of Function Primary · 12 months

Return to prior level of function will be measured by the number of days from injury to full, unrestricted return to practice. This could have occurred at any timepoint after 6 weeks, so this did not necessarily occur at 12 months but it was monitored until the 12 month timepoint.

Group	Value	95% CI
Losartan	23	14 – 42
Placebo	35	7 – 70

Recurrence of Injury Primary · 12 months

Number of recurrent injuries will be monitored during the duration of the subjects participation.

Group	Value	95% CI
Losartan	0
Placebo	2
Losartan	2
Placebo	1

Recovery of Hamstring Structure Secondary · 6 months

For specific aim 2, restoration of hamstring structure was operationally defined as the ratio of the volume of the injured to contralateral leg hamstring volume 6 months after injury 6 months post-injury. The percent of hamstring volume of the injured leg was expressed as a percentage of the hamstring volume of the contralateral normal leg. The difference in volume between the involved and non-involved hamstring muscles was divided by the non-involved hamstring muscle volume and multiplied by 100.

Group	Value	95% CI
Losartan	0.91
Placebo	3.9	-2.8 – 10.7

Return to Prior Level of Function Secondary · 4 Weeks, 6 Weeks, 3 Months, 4 Months, 6 Months, 12 Months

For specific aims 3 and 4, return to prior level of sports activity was measured by the Marx Activity Scale Score, which ranges from 0 to 16, with 16 being the highest level of sports activity. The frequency of participants who achieved the same or better Marx score at follow-up compared to baseline was calculated. Differences from baseline to each follow-up timepoint were calculated by subtracting the follow-up scores from baseline. Any difference of 0 or a negative number indicated the participants achieved the same level of sports activity or better. Positive differences indicated they did

Marx Activity Level Score: Achieved prior level or better at 4 Weeks

Group	Value	95% CI
Losartan	1
Placebo	1

Marx Activity Level Score: Achieved prior level or better at 6 Weeks

Group	Value	95% CI
Losartan	1
Placebo	1

Marx Activity Level Score: Achieved prior level or better at 3 Months

Group	Value	95% CI
Losartan	2
Placebo	3

Marx Activity Level Score: Achieved prior level or better at 4 Months

Group	Value	95% CI
Losartan	1
Placebo	3

Marx Activity Level Score: Achieved prior level or better at 6 Months

Group	Value	95% CI
Losartan	1
Placebo	1

Marx Activity Level Score: Achieved prior level or better at 12 Months

Group	Value	95% CI
Losartan	1
Placebo	1

Recovery of Hamstring Flexibility Secondary · 6 weeks; 6 months

For specific aim 2, hamstring muscle flexibility of the injured leg was measured and compared to the contralateral leg using the popliteal angle at 6 weeks and 6 months after randomization. The popliteal angle was measured with a goniometer. Recovery of hamstring flexibility was operationally defined as the difference in the popliteal angle between the contralateral normal leg minus the hamstring injured leg. Positive differences between the contralateral and injured leg indicated decreased hamstring flexibility.

Difference in popliteal angle between injured and non-injured limb at 6 weeks

Group	Value	95% CI
Losartan	1.0	-11.7 – 13.7
Placebo	-1.3	-7.1 – 4.4

Difference in popliteal angle between injured and non-injured limb at 6 months

Group	Value	95% CI
Losartan	-1.5	-20.6 – 17.6
Placebo	-0.5	-6.9 – 5.9

Recovery of Hamstring Muscle Function Secondary · 1 week; 2 weeks; 3 week; 4 weeks

For specific aim 2, hamstring muscle function of the injured leg was measured and compared to the contralateral leg using isometric hamstring force at 1 week, 2 weeks, 3 weeks, and 4 weeks. Data were expressed as a Limb Symmetry Index (LSI), which is the percent strength of the injured hamstring in comparison to the strength of the non-injured hamstring muscle.

1 week: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	70.8	0.3 – 141.2
Placebo	54.9	-37.2 – 147.1

1 week: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	83.9	62.2 – 105.6
Placebo	39.8	-59.7 – 139.2

2 weeks: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	83.3	39.8 – 126.8
Placebo	50.1	28.8 – 71.4

2 weeks: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	93.8	60.1 – 127.5
Placebo	44.6	23.1 – 66.2

3 weeks: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	103.0	-24.1 – 230.2
Placebo	87.2	47.9 – 126.4

3 weeks: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	95.9	-0.7 – 192.5
Placebo	69.1	-1.3 – 139.4

4 weeks: Limb Symmetry Index isometric strength at 30 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	79.1	45.6 – 112.7
Placebo	82.5	44.2 – 120.7

4 weeks: Limb Symmetry Index isometric strength at 90 deg knee flexion (Handheld dynamometer)

Group	Value	95% CI
Losartan	106.5	-35.3 – 248.3
Placebo	91.6	69.0 – 114.1

Recovery of Hamstring Muscle Function Secondary · 6 weeks, 6 months

For specific aim 2, hamstring muscle function of the injured leg was measured on the Biodex and compared to the contralateral leg using isokinetic peak torque at 60 degrees and 180 degrees per second at 6 weeks and 6 months. Data were expressed as a Limb Symmetry Index (LSI), which is the percent peak torque of the injured hamstring compared to the peak torque of the non-injured hamstring muscle. The isokinetic testing was not consistently collected, so there are limited results to present at 6 months.

6 Weeks: Limb Symmetry Index isokinetic peak torque at 60 deg per second (Biodex)

Group	Value	95% CI
Losartan	96.5
Placebo	202.7

6 Weeks: Limb Symmetry Index isokinetic peak torque at 180 deg per second (Biodex)

Group	Value	95% CI
Losartan	104.1
Placebo	71.2

6 Months: Limb Symmetry Index isokinetic peak torque at 60 deg per second (Biodex)

Group	Value	95% CI
Losartan	105.3

6 Months: Limb Symmetry Index isokinetic peak torque at 180 deg per second (Biodex)

Group	Value	95% CI
Losartan	81.3

Recovery of Hamstring Muscle Function Secondary · 6 weeks, 6 months

For specific aim 2, hamstring muscle function of the injured leg was measured on the Biodex and compared to the contralateral leg using isokinetic total hamstring work at 60 degrees per second and 180 degrees per second at 6 weeks and 6 months. Data were expressed as a Limb Symmetry Index (LSI), which is the percent total work of the injured hamstring compared to the total work of the non-injured hamstring muscle. The isokinetic testing was not consistently collected, so there are limited results to present at 6 months.

6 Weeks: Limb Symmetry Index isokinetic total hamstring work at 60 deg per second (Biodex)

Group	Value	95% CI
Losartan	108.9
Placebo	484.2

6 Weeks: Limb Symmetry Index isokinetic total hamstring work at 180 deg per second (Biodex)

Group	Value	95% CI
Losartan	134.2
Placebo	63.3

6 Months: Limb Symmetry Index isokinetic total hamstring work at 60 deg per second (Biodex)

Group	Value	95% CI
Losartan	113.8

6 Months: Limb Symmetry Index isokinetic total hamstring work at 180 deg per second (Biodex)

Group	Value	95% CI
Losartan	78.9

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Losartan

Serious: 0/3 (0%)

Deaths: 0/3

Placebo

Serious: 0/3 (0%)

Deaths: 0/3

Other adverse events (1 terms — click to expand)

Reaction	System	Losartan	Placebo
Hamstring reinjury	Musculoskeletal and connective tissue disorders	—	—

Data from ClinicalTrials.gov NCT02263729 adverse events section.

Sponsor's own description

The goal of this study is to determine safety and tolerability of Losartan when used for treatment of an acute grade II or III hamstring strain and determining the effect of losartan on recovery of hamstring muscle function. Subjects will be adults age 18 and older with grade 2 or 3 hamstring injury who participate in greater than 100 hours per year in Level 1 or Level 2 athletics or have a similar activities or physical work load (e.g. military personnel). Subjects will undergo examination, MRI, and functional assessment before, during, and after 4 weeks of losartan (50mg QD) or placebo.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Losartan to Improve Outcomes after multi-ligament kNee injury (LION Trial).
   Kehoe S, Stone A, Yuan X, Conley C, et al · · 2026 · PMID 41981668 · DOI 10.1186/s13063-026-09714-3