Actovegin 12-Week Treatment Given First Intravenously and Subsequently Orally in Participants With Peripheral Arterial Occlusive Disease Fontaine Stage IIB

Peripheral Arterial Diseases Clinical Trial

— APOLLO  

Official title:

A Randomized, International, Multicenter, Parallel Group, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Actovegin 12-Week Treatment Given First Intravenously and Subsequently Orally in Subjects With Peripheral Arterial Occlusive Disease Fontaine Stage IIB

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03469349
• Other study ID #: Actovegin-3001
• Secondary ID: 2017-004741-24U1
• Status: Completed
• Phase: Phase 3
• Start date: May 1, 2018
• Est. completion date: August 28, 2019

Study information

• Verified date: October 2020
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the efficacy and safety of actovegin in participants with peripheral arterial disease (PAD) Fontaine Stage IIB.

Description:

The study will enroll approximately 366 participants. Participants will be randomly assigned to one of the two treatment groups in 1:1 ratio:

1. Actovegin

2. Placebo (dummy inactive substance) - this is a tablet/intravenous infusion that looks like the study drug but has no active ingredient

All participants will be asked to take intravenous infusion for 2 weeks followed by oral tablets for 10 weeks.

This multi-center trial will be conducted Russia, Georgia, and Kazakhstan. The overall time to participate in this study is 25 to 26 weeks. Participants will make multiple visits to the clinic, and 12 weeks after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 366
• Est. completion date: August 28, 2019
• Est. primary completion date: May 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Has a history of stable intermittent claudication lasting more than 6 months before Screening.

2. Has a diagnosis of peripheral arterial disease (PAD) (Code I70.2 according to the international classification of diseases-10th revision) Fontaine Stage IIB confirmed by ultrasound color duplex imaging.

3. Has a resting Doppler ankle-brachial index of less than or equal to (<=) 0.9.

4. Has intermittent claudication with initial claudication distance (ICD) less than (<) 200 meters.

5. Is not newly diagnosed with PAD and has a history of stable PAD therapy for at least 2 weeks before Screening.

Exclusion Criteria:

1. Has PAD Fontaine Stage III or IV (pain at rest, non-healing ulceration, or gangrene).

2. Has evidence of nonatherosclerotic PAD.

3. Has greater than (>) 25 percent (%) variability in absolute claudication distance (ACD) based on treadmill testing during the screening period.

4. Has lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within 3 months before Screening.

5. Is eligible for surgical/interventional reconstruction.

6. Had a myocardial infarction or major cardiac surgery within 3 months before Screening.

7. Has congestive heart failure (New York Heart Association Class III/IV).

8. Has uncontrolled diabetes mellitus (glycosylated hemoglobin [HbA1c >9%]) or diabetic polyneuropathy.

9. Has any other illness that significantly limits exercise capacity or other medical condition, including any psychiatric disorder that limits participation (in the judgement of the investigator).

10. The subject has received any prohibited medication within 14 days before Randomization (Day 1)

11. The subject is undergoing the supervised exercise training program by the time of Screening and is going to continue this program due to its effectiveness.

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Peripheral Arterial Disease
• Peripheral Arterial Diseases
• Peripheral Vascular Diseases

Intervention

Drug:
• Actovegin
Actovegin intravenous infusion and tablets.
• Placebo
Actovegin placebo-matching intravenous infusion and tablets.

Locations

Country	Name	City	State
Georgia	Aversi Clinic	Tbilisi
Georgia	Center of Vascular and Heart Disease	Tbilisi
Kazakhstan	"National scientific centre of oncology and transplantology"	Astana
Kazakhstan	Regional Clinic Hospital	Shymkent
Russian Federation	NSHI Road clinical hospital at Chelyabinsk station of OAO RZD	Chelyabinsk
Russian Federation	Federal state budgetary research institution Research Institute for Complex Issues of Cardiovascular Diseases	Kemerovo
Russian Federation	BMH Kursk regional clinical hospital of Healthcare department of Kursk region	Kursk
Russian Federation	SBHI of Moscow city "City clinical hospital #29 n.a. N.E. Bauman of Moscow Healthcare department	Moscow
Russian Federation	SBHI of Moscow healthcare department City clinical hospital #15 n.a. O.M Filatov of Moscow healthcare department	Moscow
Russian Federation	SBHI of Moscow Research Institute of Emergency Medicine n.a. N.V. Sklifosofsky of Moscow Healthcare department	Moscow
Russian Federation	Scientific Research Institute of Clinical and Experimental Lymphology - a branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences	Novosibirsk
Russian Federation	BHI of Omsk region Regional clinical hospital, vessel surgery department	Omsk
Russian Federation	FSBEI HE Rostov State Medical University of MoH of Russia	Rostov-on-Don
Russian Federation	SBHI of Ryazan region Regional clinical cardiological dispensary, vessel surgery department/ FSBI of Ryazan Region "Ryazan State Medical Univesity n.a. I.P. Pavlov" of MoH of Russia	Ryazan
Russian Federation	Pavlov First Saint Petersburg State Medical University, Faculty surgery chair, cardio-vessel surgery department	Saint Petersburg
Russian Federation	SPb SBHI Consulting and diagnostic center #85	Saint Petersburg
Russian Federation	North-Western State Medical University named after I.I. Mechnikov	Saint-Petersburg
Russian Federation	SPb SBHI City multipurpose hospital #2	Saint-Petersburg
Russian Federation	State Healthcare Institution of Saratov region "Region clinical hospitai"	Saratov
Russian Federation	Municipal State Budgetary Healthcare Institution of Sochi "City hospital 4"	Sochi

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

Georgia,  Kazakhstan,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Initial Claudication Distance (ICD) at Week 12	ICD was the distance walked at the onset of claudication pain or pain-free walking distance. ICD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 kilometer per hour (km/h) with a 10 percent (%) grade.	Baseline up to Week 12
Secondary	Percent Change From Baseline in ICD at Weeks 2 and 24	ICD was the distance walked at the onset of claudication pain or pain-free walking distance. ICD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 km/h with a 10% grade.	Baseline up to Weeks 2 and 24
Secondary	Absolute Change From Baseline in Absolute Claudication Distance (ACD) at Weeks 2, 12 and 24	ACD was the distance at which claudication pain becomes so severe that the participant was forced to stop, also known as maximal walking distance. ACD was assessed using treadmill testing. A fixed load treadmill test was carried out at 3.0 km/h with a 10% grade. The investigator will record the distance from walking start to the point where the participant is unable to walk anymore.	Baseline, Weeks 2, 12 and 24
Secondary	Percentage of Participants With Rest Pain at Weeks 12 and 24	Rest pain was defined as a continuous burning pain, that begins, or is aggravated, after reclining or elevating the limb and is relieved by sitting or standing.	Weeks 12 and 24
Secondary	Percentage of Participants With Revascularization Procedures at Week 24	Revascularization was defined by a Thrombolysis in Myocardial Infarction (TIMI) score of 2 or 3 following use of the Penumbra System. TIMI scores were used to describe blood flow at the treated vessel with 0 designating no flow and 3 for normal flow.	Week 24
Secondary	Change From Baseline in 36-Item Short Form Survey (SF-36) at Weeks 12 and 24	The SF-36 was a questionnaire that evaluated a participant's health related quality of life. SF-36 included 36 questions related to 8 health dimensions: physical functioning, role-physical (role limitations due to physical health problems), bodily pain, general health, vitality (energy/fatigue), social functioning, role-emotional (role limitations due to emotional problems), and mental health. Based on these 4 scales (physical functioning, role-physical, bodily pain, general health), the physical health score was generated which ranges between 0 and 100, with higher scores indicating a better quality of life. Based on these 4 scales (vitality, social functioning, role-emotional, and mental health), the mental health score was generated which ranges between 0 and 100, with higher scores indicating a better quality of life.	Baseline, Weeks 12 and 24